A high proportion of SARS-CoV-2–infected university students are asymptomatic

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A high proportion of SARS-CoV-2–infected university students are asymptomatic

Many individuals infected with SARS-CoV-2 never become symptomatic. In a South Korean study, these infected individuals remained asymptomatic for a prolonged period while maintaining the same viral load as symptomatic patients, suggesting that they are just as infectious.1 A narrative review found high rates of asymptomatic disease in several younger populations, including women in an obstetric ward (88%), the crew of an aircraft carrier (58%), and prisoners (96%).2 However, there is no published research on the percentage of university students who are asymptomatic.

Methods 

The University of Georgia (UGA) began classes on August 20, 2020. Shortly before the beginning of classes, UGA implemented a surveillance program for asymptomatic students, faculty, and staff, testing 300 to 450 people per day. Initially, during Weeks 1 and 2 of data collection, anyone could choose to be tested. In Weeks 3 and 4, students, faculty, and staff were randomly invited to participate.

The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.

Over the 4-week period beginning on August 17, we calculated the percent of positive cases in surveillance testing and applied this percentage to the entire UGA student population (n = 38,920) to estimate the total number of asymptomatic COVID-19 students each week.3 Data for symptomatic cases were also reported by the university on a weekly basis. This included positive tests from the University Health Center, as well as voluntary reporting using a smartphone app from other sites.

 

Positive tests in symptomatic individuals were not stratified by student vs nonstudent until Week 3; students comprised 95% of positive symptomatic reports in Week 3 and 99% in Week 4, so we conservatively estimated that 95% of symptomatic cases in Weeks 1 and 2 were students. These data were used to estimate the percentage of SARS-CoV-2–positive students who were asymptomatic. 

Results

Our results are summarized in the table. The percentage of asymptomatic students testing positive in surveillance testing was 3.4% in Week 1 and rose steadily to 9% by Week 4. We estimated that there were 1303 asymptomatic cases among students in Week 1, increasing to 3487 asymptomatic positive students on campus by Week 4. The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.

SARS-CoV-2 infection: Symptomatic student cases and surveillance of asymptomatic students at the University of Georgia

Discussion

During the reporting period from August 17 to September 13, the 7-day moving average of new cases in Clarke County (home of UGA) increased from 30 to 83 per 100,000 persons/day (https://dph.georgia.gov/covid-19-daily-status-report). During this period, there were large increases in the number of infected students, more than 80% of whom were asymptomatic. With the assumption that anyone could be infected even if asymptomatic, these numbers highlight the importance for infection control to prevent potential spread within a community by taking universal precautions such as wearing a mask, following physical distancing guidelines, and handwashing.

Limitations. First, reporting of positive tests in symptomatic individuals is highly encouraged but not required. The large drop in symptomatic positive test reports between Weeks 3 and 4, with no change in test positivity in surveillance of asymptomatic students (8.9% vs 9%), suggests that students may have chosen to be tested elsewhere in conjunction with evaluation of their symptoms and/or not reported positive tests, possibly to avoid mandatory isolation and other restrictions on their activities. Further evidence to support no change in actual infection rates comes from testing for virus in wastewater, which also remained unchanged.4

Continue to: Second, each week's surveillance...

 

 

Second, each week’s surveillance population is not a true random sample, so extrapolating this estimate to the full student population could over- or undercount asymptomatic cases depending on the direction of bias (ie, healthy volunteer bias vs test avoidance by those with high-risk behaviors).

Finally, some students who were positive in surveillance testing may have been presymptomatic, rather than asymptomatic.

In conclusion, we estimate that approximately 80% of students infected with SARS-CoV-2 are asymptomatic. This is consistent with other studies in young adult populations.2

Mark H. Ebell, MD, MS
Cassie Chupp, MPH
Michelle Bentivegna, MPH

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens
ebell@uga.edu

The authors reported no potential conflict of interest relevant to this article.

References

1. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea [published online ahead of print August 6, 2020]. JAMA Intern Med. doi:10.1001/jamainternmed.2020.3862

2. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review. Ann Intern Med. 2020;173:362-367.

3. UGA by the Numbers. University of Georgia Web site. www.uga.edu/facts.php. Updated August 2020. Accessed October 20, 2020.

4. Lott M, Norfolk W, Robertson M, et al. Wastewater surveillance for SARS-CoV-2 in Athens, GA. COVID-19 Portal: Center for the Ecology of Infectious Diseases, University of Georgia Web site. www.covid19.uga.edu/wastewater-athens.html. Updated October 15, 2020. Accessed October 20, 2020.

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Many individuals infected with SARS-CoV-2 never become symptomatic. In a South Korean study, these infected individuals remained asymptomatic for a prolonged period while maintaining the same viral load as symptomatic patients, suggesting that they are just as infectious.1 A narrative review found high rates of asymptomatic disease in several younger populations, including women in an obstetric ward (88%), the crew of an aircraft carrier (58%), and prisoners (96%).2 However, there is no published research on the percentage of university students who are asymptomatic.

Methods 

The University of Georgia (UGA) began classes on August 20, 2020. Shortly before the beginning of classes, UGA implemented a surveillance program for asymptomatic students, faculty, and staff, testing 300 to 450 people per day. Initially, during Weeks 1 and 2 of data collection, anyone could choose to be tested. In Weeks 3 and 4, students, faculty, and staff were randomly invited to participate.

The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.

Over the 4-week period beginning on August 17, we calculated the percent of positive cases in surveillance testing and applied this percentage to the entire UGA student population (n = 38,920) to estimate the total number of asymptomatic COVID-19 students each week.3 Data for symptomatic cases were also reported by the university on a weekly basis. This included positive tests from the University Health Center, as well as voluntary reporting using a smartphone app from other sites.

 

Positive tests in symptomatic individuals were not stratified by student vs nonstudent until Week 3; students comprised 95% of positive symptomatic reports in Week 3 and 99% in Week 4, so we conservatively estimated that 95% of symptomatic cases in Weeks 1 and 2 were students. These data were used to estimate the percentage of SARS-CoV-2–positive students who were asymptomatic. 

Results

Our results are summarized in the table. The percentage of asymptomatic students testing positive in surveillance testing was 3.4% in Week 1 and rose steadily to 9% by Week 4. We estimated that there were 1303 asymptomatic cases among students in Week 1, increasing to 3487 asymptomatic positive students on campus by Week 4. The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.

SARS-CoV-2 infection: Symptomatic student cases and surveillance of asymptomatic students at the University of Georgia

Discussion

During the reporting period from August 17 to September 13, the 7-day moving average of new cases in Clarke County (home of UGA) increased from 30 to 83 per 100,000 persons/day (https://dph.georgia.gov/covid-19-daily-status-report). During this period, there were large increases in the number of infected students, more than 80% of whom were asymptomatic. With the assumption that anyone could be infected even if asymptomatic, these numbers highlight the importance for infection control to prevent potential spread within a community by taking universal precautions such as wearing a mask, following physical distancing guidelines, and handwashing.

Limitations. First, reporting of positive tests in symptomatic individuals is highly encouraged but not required. The large drop in symptomatic positive test reports between Weeks 3 and 4, with no change in test positivity in surveillance of asymptomatic students (8.9% vs 9%), suggests that students may have chosen to be tested elsewhere in conjunction with evaluation of their symptoms and/or not reported positive tests, possibly to avoid mandatory isolation and other restrictions on their activities. Further evidence to support no change in actual infection rates comes from testing for virus in wastewater, which also remained unchanged.4

Continue to: Second, each week's surveillance...

 

 

Second, each week’s surveillance population is not a true random sample, so extrapolating this estimate to the full student population could over- or undercount asymptomatic cases depending on the direction of bias (ie, healthy volunteer bias vs test avoidance by those with high-risk behaviors).

Finally, some students who were positive in surveillance testing may have been presymptomatic, rather than asymptomatic.

In conclusion, we estimate that approximately 80% of students infected with SARS-CoV-2 are asymptomatic. This is consistent with other studies in young adult populations.2

Mark H. Ebell, MD, MS
Cassie Chupp, MPH
Michelle Bentivegna, MPH

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens
ebell@uga.edu

The authors reported no potential conflict of interest relevant to this article.

Many individuals infected with SARS-CoV-2 never become symptomatic. In a South Korean study, these infected individuals remained asymptomatic for a prolonged period while maintaining the same viral load as symptomatic patients, suggesting that they are just as infectious.1 A narrative review found high rates of asymptomatic disease in several younger populations, including women in an obstetric ward (88%), the crew of an aircraft carrier (58%), and prisoners (96%).2 However, there is no published research on the percentage of university students who are asymptomatic.

Methods 

The University of Georgia (UGA) began classes on August 20, 2020. Shortly before the beginning of classes, UGA implemented a surveillance program for asymptomatic students, faculty, and staff, testing 300 to 450 people per day. Initially, during Weeks 1 and 2 of data collection, anyone could choose to be tested. In Weeks 3 and 4, students, faculty, and staff were randomly invited to participate.

The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.

Over the 4-week period beginning on August 17, we calculated the percent of positive cases in surveillance testing and applied this percentage to the entire UGA student population (n = 38,920) to estimate the total number of asymptomatic COVID-19 students each week.3 Data for symptomatic cases were also reported by the university on a weekly basis. This included positive tests from the University Health Center, as well as voluntary reporting using a smartphone app from other sites.

 

Positive tests in symptomatic individuals were not stratified by student vs nonstudent until Week 3; students comprised 95% of positive symptomatic reports in Week 3 and 99% in Week 4, so we conservatively estimated that 95% of symptomatic cases in Weeks 1 and 2 were students. These data were used to estimate the percentage of SARS-CoV-2–positive students who were asymptomatic. 

Results

Our results are summarized in the table. The percentage of asymptomatic students testing positive in surveillance testing was 3.4% in Week 1 and rose steadily to 9% by Week 4. We estimated that there were 1303 asymptomatic cases among students in Week 1, increasing to 3487 asymptomatic positive students on campus by Week 4. The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.

SARS-CoV-2 infection: Symptomatic student cases and surveillance of asymptomatic students at the University of Georgia

Discussion

During the reporting period from August 17 to September 13, the 7-day moving average of new cases in Clarke County (home of UGA) increased from 30 to 83 per 100,000 persons/day (https://dph.georgia.gov/covid-19-daily-status-report). During this period, there were large increases in the number of infected students, more than 80% of whom were asymptomatic. With the assumption that anyone could be infected even if asymptomatic, these numbers highlight the importance for infection control to prevent potential spread within a community by taking universal precautions such as wearing a mask, following physical distancing guidelines, and handwashing.

Limitations. First, reporting of positive tests in symptomatic individuals is highly encouraged but not required. The large drop in symptomatic positive test reports between Weeks 3 and 4, with no change in test positivity in surveillance of asymptomatic students (8.9% vs 9%), suggests that students may have chosen to be tested elsewhere in conjunction with evaluation of their symptoms and/or not reported positive tests, possibly to avoid mandatory isolation and other restrictions on their activities. Further evidence to support no change in actual infection rates comes from testing for virus in wastewater, which also remained unchanged.4

Continue to: Second, each week's surveillance...

 

 

Second, each week’s surveillance population is not a true random sample, so extrapolating this estimate to the full student population could over- or undercount asymptomatic cases depending on the direction of bias (ie, healthy volunteer bias vs test avoidance by those with high-risk behaviors).

Finally, some students who were positive in surveillance testing may have been presymptomatic, rather than asymptomatic.

In conclusion, we estimate that approximately 80% of students infected with SARS-CoV-2 are asymptomatic. This is consistent with other studies in young adult populations.2

Mark H. Ebell, MD, MS
Cassie Chupp, MPH
Michelle Bentivegna, MPH

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens
ebell@uga.edu

The authors reported no potential conflict of interest relevant to this article.

References

1. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea [published online ahead of print August 6, 2020]. JAMA Intern Med. doi:10.1001/jamainternmed.2020.3862

2. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review. Ann Intern Med. 2020;173:362-367.

3. UGA by the Numbers. University of Georgia Web site. www.uga.edu/facts.php. Updated August 2020. Accessed October 20, 2020.

4. Lott M, Norfolk W, Robertson M, et al. Wastewater surveillance for SARS-CoV-2 in Athens, GA. COVID-19 Portal: Center for the Ecology of Infectious Diseases, University of Georgia Web site. www.covid19.uga.edu/wastewater-athens.html. Updated October 15, 2020. Accessed October 20, 2020.

References

1. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea [published online ahead of print August 6, 2020]. JAMA Intern Med. doi:10.1001/jamainternmed.2020.3862

2. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review. Ann Intern Med. 2020;173:362-367.

3. UGA by the Numbers. University of Georgia Web site. www.uga.edu/facts.php. Updated August 2020. Accessed October 20, 2020.

4. Lott M, Norfolk W, Robertson M, et al. Wastewater surveillance for SARS-CoV-2 in Athens, GA. COVID-19 Portal: Center for the Ecology of Infectious Diseases, University of Georgia Web site. www.covid19.uga.edu/wastewater-athens.html. Updated October 15, 2020. Accessed October 20, 2020.

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Medication adherence challenges and helpers

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Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.1 Most apps focus on medication alerts, reminders, and medication logs.2 A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.3

Dr. Chris Notte and Dr. Neil Skolnik

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.4

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,5 as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.6 Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.7 This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.7

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

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Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.1 Most apps focus on medication alerts, reminders, and medication logs.2 A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.3

Dr. Chris Notte and Dr. Neil Skolnik

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.4

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,5 as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.6 Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.7 This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.7

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.1 Most apps focus on medication alerts, reminders, and medication logs.2 A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.3

Dr. Chris Notte and Dr. Neil Skolnik

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.4

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,5 as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.6 Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.7 This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.7

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

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Response to “The Other Pandemic: Addiction”

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To the Editor: Normally I would skip the editorial; however, the title “The Other Pandemic: Addiction” caught my eye (Fed Pract. 2020;37[10]:440-441). This will, of course, require me going in for eye care in the next couple of days, but my concerns are low. After all, the hook you used wasn’t that big.

Bravo! Your choice to focus on the effects of isolation was a masterful touch. I started skimming with the assumption that you would say something along the lines of ‘COVID bad, everybody depressed, blah, blah.’ But you cut into the abscess of the issue cleanly, exposing the core—isolation “amplifies negative thoughts, dysphoria, and fearful emotions.” A deadly combination for our patients and ourselves.

I have been a physician assistant in the US Army, and as a civilian at Brooke Army Medical Center and US Department of Veterans Affairs (VA) Puget Sound Health Care System. One thing I have seen throughout that time was the effects of isolation on the active duty enlisted young, and even more so on retired older warriors. Throughout the time of our military service, we transfer to many places and make a lot of friends, but more so, we lose track of them over time.

I have cared for many older warriors who cannot get something as simple as a colonoscopy because they do not have someone to drive them home after they have been sedated. Family and friends were scattered over the country, or the world. At the VA, many older warriors come not just for an appointment, but also as a time to socialize and ‘BS’ with those who understand them.

One goal I set for myself many years ago was to have the warrior laughing before they left my office. If I did that, I knew I had made a difference. Thank you for your editorial.

Anthony J Passaniti, PA, USA (ret) ajp78232@gmail.com

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To the Editor: Normally I would skip the editorial; however, the title “The Other Pandemic: Addiction” caught my eye (Fed Pract. 2020;37[10]:440-441). This will, of course, require me going in for eye care in the next couple of days, but my concerns are low. After all, the hook you used wasn’t that big.

Bravo! Your choice to focus on the effects of isolation was a masterful touch. I started skimming with the assumption that you would say something along the lines of ‘COVID bad, everybody depressed, blah, blah.’ But you cut into the abscess of the issue cleanly, exposing the core—isolation “amplifies negative thoughts, dysphoria, and fearful emotions.” A deadly combination for our patients and ourselves.

I have been a physician assistant in the US Army, and as a civilian at Brooke Army Medical Center and US Department of Veterans Affairs (VA) Puget Sound Health Care System. One thing I have seen throughout that time was the effects of isolation on the active duty enlisted young, and even more so on retired older warriors. Throughout the time of our military service, we transfer to many places and make a lot of friends, but more so, we lose track of them over time.

I have cared for many older warriors who cannot get something as simple as a colonoscopy because they do not have someone to drive them home after they have been sedated. Family and friends were scattered over the country, or the world. At the VA, many older warriors come not just for an appointment, but also as a time to socialize and ‘BS’ with those who understand them.

One goal I set for myself many years ago was to have the warrior laughing before they left my office. If I did that, I knew I had made a difference. Thank you for your editorial.

Anthony J Passaniti, PA, USA (ret) ajp78232@gmail.com

To the Editor: Normally I would skip the editorial; however, the title “The Other Pandemic: Addiction” caught my eye (Fed Pract. 2020;37[10]:440-441). This will, of course, require me going in for eye care in the next couple of days, but my concerns are low. After all, the hook you used wasn’t that big.

Bravo! Your choice to focus on the effects of isolation was a masterful touch. I started skimming with the assumption that you would say something along the lines of ‘COVID bad, everybody depressed, blah, blah.’ But you cut into the abscess of the issue cleanly, exposing the core—isolation “amplifies negative thoughts, dysphoria, and fearful emotions.” A deadly combination for our patients and ourselves.

I have been a physician assistant in the US Army, and as a civilian at Brooke Army Medical Center and US Department of Veterans Affairs (VA) Puget Sound Health Care System. One thing I have seen throughout that time was the effects of isolation on the active duty enlisted young, and even more so on retired older warriors. Throughout the time of our military service, we transfer to many places and make a lot of friends, but more so, we lose track of them over time.

I have cared for many older warriors who cannot get something as simple as a colonoscopy because they do not have someone to drive them home after they have been sedated. Family and friends were scattered over the country, or the world. At the VA, many older warriors come not just for an appointment, but also as a time to socialize and ‘BS’ with those who understand them.

One goal I set for myself many years ago was to have the warrior laughing before they left my office. If I did that, I knew I had made a difference. Thank you for your editorial.

Anthony J Passaniti, PA, USA (ret) ajp78232@gmail.com

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Why Accept a VA Detail or Short-Term Assignment? Benefits to Employees and the Service

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In the Veterans Health Administration (VHA), there are frequent e-mails and requests for employees to accept a detail or short-term assignment across a wide range of positions from administrative to executive leadership. These opportunities afford an employee and the service line valuable benefits and growth opportunities; however, there are reasons why some may be reluctant to pursue these opportunities. In this article, we discuss the barriers to applying for and accepting detail positions and the benefits for the employee and the service lines during periods of standard operations as well as during emergencies requiring alternative staffing strategies.

Details are short-term assignments used to fill a vacant position while hiring for the permanent position or to fill a short-term need (eg, during a pandemic). Details usually last 30 to 120 days, though they may be extended, depending on the position, the number of people willing to serve in the detailed role, and the time to select a candidate for the permanent position. Details can be created for any skill level or type of position to meet an identified need, but they are most often needed for supervisory or leadership roles.

The COVID-19 pandemic has shed light on the importance of individuals’ flexibility and adaptability both within and between roles. Many US Department of Veterans Affairs (VA) facilities stood up Incident Command structures to support the changes required to adapt to the needs created by the pandemic. Establishing an Incident Command means that people within the organization must take on new responsibilities, and in many cases, they are detailed to new positions that were not needed or prioritized before the pandemic.

Barriers

An employee may be reluctant to apply for or accept a detail because he or she has little to no experience; feels uncomfortable stepping into an unfamiliar role; is concerned about making a leap from a clinical to administrative role; has uncertainty whether the job is a good professional fit; dislikes the lack of a pay increase during the detail period even if the new role has more responsibility; and has concern that serving in the detail may make them ineligible to apply for the permanent position due to a perception of being preselected. Additionally, the employee may recognize the added stress on colleagues because the same amount of work must be completed.

Benefits

Although leaving a position for a period of months can be stressful, serving in a detail position provides significant opportunities for professional growth. An employee can gain knowledge and experience in an unfamiliar role before applying for or committing to a permanent position. Those serving in temporary details are often given more support as colleagues and supervisors understand that the role was accepted on short notice with little time to prepare. Other benefits include expanding professional contacts, gaining perspective on a different part of the VHA, and working on skills, such as flexibility, time management, and perseverance. By succeeding in a detail, employees build professional acumen. After taking on additional challenges they become more competitive for future jobs. The VHA Executive Candidate Development Program requires a 120-day detail, serving as either assistant or associate director, chief of staff, or associate director for patient care services/nurse executive as part of the program.1

 

 

Temporarily leaving a service line to detail in a different service line has an impact on the home service because of the restrictions imposed. These restrictions guarantee that the employee can return to the original position at the end of a detail, thus providing a sense of job security; however, the home service line is down an employee.

Given these considerations, the following are key points to establish before undertaking the detail: (1) length of assignment; (2) once started, potential for the assignment to be extended; (3) will the employee be doing any of their prior job or just the new job or a blend of both; (4) possible changes in hours and site of work of the employee; (5) who will supervise the employee; (6) who will write the employee’s review; (7) training or skills needed prior to starting; (8) necessary paperwork; (9) how will the new assignment be communicated to others; (10) what happens if the detail ends sooner than planned; and (11) approval and support of all involved parties.

The employee’s home service may need a temporary plan to cover the employee’s workload, especially if the employee will be detailed to a different service line. The temporary plan may require creativity and flexibility and can be a way to trial the contingency plans for staffing the home service. One benefit to the home service is that the employee will have additional skills on returning that may benefit the home service, and the service will gain a potential leader.

When an employee goes to a different service, that service gains an employee who may bring a new perspective to help solve existing conflicts or problems. This can serve as a time to reset expectations or set new goals prior to the arrival of new leadership. If the detail is a good fit, then there is the chance that the employee may return in the future or refer others to it as a professional opportunity.

Conclusions

A detail can benefit the employee and the home and host services if planned in advance, and all parties support the process. A short-term leadership or administrative assignment can help an employee gain valuable experience for the future.

References

1. US Department of Veterans Affairs. Improve VA’s employee experience.obamaadministration.archives.performance.gov/node/65741.html. Published 2017. Accessed October 19, 2020.

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Wendy Henderson is Associate Chief of Staff (Ambulatory Care Service), and Genevieve Embree is a Staff Physician and Deputy Chief of the Office of Public Health/Epidemiology, Public Health Liaison/ Community Support, both at the Durham VA Health Care System. Wendy Henderson is an Assistant Professor, and Genevieve Embree is a Medical Instructor in the Department of Medicine, both at Duke University in North Carolina.
 Correspondence: Wendy Henderson (wendy.henderson@ va.gov)

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The authors report no actual or potential conflicts of interest with regard to this article.

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner , Frontline Medical Communications Inc., the US Government, or any of its agencies.

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Wendy Henderson is Associate Chief of Staff (Ambulatory Care Service), and Genevieve Embree is a Staff Physician and Deputy Chief of the Office of Public Health/Epidemiology, Public Health Liaison/ Community Support, both at the Durham VA Health Care System. Wendy Henderson is an Assistant Professor, and Genevieve Embree is a Medical Instructor in the Department of Medicine, both at Duke University in North Carolina.
 Correspondence: Wendy Henderson (wendy.henderson@ va.gov)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner , Frontline Medical Communications Inc., the US Government, or any of its agencies.

Author and Disclosure Information

Wendy Henderson is Associate Chief of Staff (Ambulatory Care Service), and Genevieve Embree is a Staff Physician and Deputy Chief of the Office of Public Health/Epidemiology, Public Health Liaison/ Community Support, both at the Durham VA Health Care System. Wendy Henderson is an Assistant Professor, and Genevieve Embree is a Medical Instructor in the Department of Medicine, both at Duke University in North Carolina.
 Correspondence: Wendy Henderson (wendy.henderson@ va.gov)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner , Frontline Medical Communications Inc., the US Government, or any of its agencies.

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In the Veterans Health Administration (VHA), there are frequent e-mails and requests for employees to accept a detail or short-term assignment across a wide range of positions from administrative to executive leadership. These opportunities afford an employee and the service line valuable benefits and growth opportunities; however, there are reasons why some may be reluctant to pursue these opportunities. In this article, we discuss the barriers to applying for and accepting detail positions and the benefits for the employee and the service lines during periods of standard operations as well as during emergencies requiring alternative staffing strategies.

Details are short-term assignments used to fill a vacant position while hiring for the permanent position or to fill a short-term need (eg, during a pandemic). Details usually last 30 to 120 days, though they may be extended, depending on the position, the number of people willing to serve in the detailed role, and the time to select a candidate for the permanent position. Details can be created for any skill level or type of position to meet an identified need, but they are most often needed for supervisory or leadership roles.

The COVID-19 pandemic has shed light on the importance of individuals’ flexibility and adaptability both within and between roles. Many US Department of Veterans Affairs (VA) facilities stood up Incident Command structures to support the changes required to adapt to the needs created by the pandemic. Establishing an Incident Command means that people within the organization must take on new responsibilities, and in many cases, they are detailed to new positions that were not needed or prioritized before the pandemic.

Barriers

An employee may be reluctant to apply for or accept a detail because he or she has little to no experience; feels uncomfortable stepping into an unfamiliar role; is concerned about making a leap from a clinical to administrative role; has uncertainty whether the job is a good professional fit; dislikes the lack of a pay increase during the detail period even if the new role has more responsibility; and has concern that serving in the detail may make them ineligible to apply for the permanent position due to a perception of being preselected. Additionally, the employee may recognize the added stress on colleagues because the same amount of work must be completed.

Benefits

Although leaving a position for a period of months can be stressful, serving in a detail position provides significant opportunities for professional growth. An employee can gain knowledge and experience in an unfamiliar role before applying for or committing to a permanent position. Those serving in temporary details are often given more support as colleagues and supervisors understand that the role was accepted on short notice with little time to prepare. Other benefits include expanding professional contacts, gaining perspective on a different part of the VHA, and working on skills, such as flexibility, time management, and perseverance. By succeeding in a detail, employees build professional acumen. After taking on additional challenges they become more competitive for future jobs. The VHA Executive Candidate Development Program requires a 120-day detail, serving as either assistant or associate director, chief of staff, or associate director for patient care services/nurse executive as part of the program.1

 

 

Temporarily leaving a service line to detail in a different service line has an impact on the home service because of the restrictions imposed. These restrictions guarantee that the employee can return to the original position at the end of a detail, thus providing a sense of job security; however, the home service line is down an employee.

Given these considerations, the following are key points to establish before undertaking the detail: (1) length of assignment; (2) once started, potential for the assignment to be extended; (3) will the employee be doing any of their prior job or just the new job or a blend of both; (4) possible changes in hours and site of work of the employee; (5) who will supervise the employee; (6) who will write the employee’s review; (7) training or skills needed prior to starting; (8) necessary paperwork; (9) how will the new assignment be communicated to others; (10) what happens if the detail ends sooner than planned; and (11) approval and support of all involved parties.

The employee’s home service may need a temporary plan to cover the employee’s workload, especially if the employee will be detailed to a different service line. The temporary plan may require creativity and flexibility and can be a way to trial the contingency plans for staffing the home service. One benefit to the home service is that the employee will have additional skills on returning that may benefit the home service, and the service will gain a potential leader.

When an employee goes to a different service, that service gains an employee who may bring a new perspective to help solve existing conflicts or problems. This can serve as a time to reset expectations or set new goals prior to the arrival of new leadership. If the detail is a good fit, then there is the chance that the employee may return in the future or refer others to it as a professional opportunity.

Conclusions

A detail can benefit the employee and the home and host services if planned in advance, and all parties support the process. A short-term leadership or administrative assignment can help an employee gain valuable experience for the future.

In the Veterans Health Administration (VHA), there are frequent e-mails and requests for employees to accept a detail or short-term assignment across a wide range of positions from administrative to executive leadership. These opportunities afford an employee and the service line valuable benefits and growth opportunities; however, there are reasons why some may be reluctant to pursue these opportunities. In this article, we discuss the barriers to applying for and accepting detail positions and the benefits for the employee and the service lines during periods of standard operations as well as during emergencies requiring alternative staffing strategies.

Details are short-term assignments used to fill a vacant position while hiring for the permanent position or to fill a short-term need (eg, during a pandemic). Details usually last 30 to 120 days, though they may be extended, depending on the position, the number of people willing to serve in the detailed role, and the time to select a candidate for the permanent position. Details can be created for any skill level or type of position to meet an identified need, but they are most often needed for supervisory or leadership roles.

The COVID-19 pandemic has shed light on the importance of individuals’ flexibility and adaptability both within and between roles. Many US Department of Veterans Affairs (VA) facilities stood up Incident Command structures to support the changes required to adapt to the needs created by the pandemic. Establishing an Incident Command means that people within the organization must take on new responsibilities, and in many cases, they are detailed to new positions that were not needed or prioritized before the pandemic.

Barriers

An employee may be reluctant to apply for or accept a detail because he or she has little to no experience; feels uncomfortable stepping into an unfamiliar role; is concerned about making a leap from a clinical to administrative role; has uncertainty whether the job is a good professional fit; dislikes the lack of a pay increase during the detail period even if the new role has more responsibility; and has concern that serving in the detail may make them ineligible to apply for the permanent position due to a perception of being preselected. Additionally, the employee may recognize the added stress on colleagues because the same amount of work must be completed.

Benefits

Although leaving a position for a period of months can be stressful, serving in a detail position provides significant opportunities for professional growth. An employee can gain knowledge and experience in an unfamiliar role before applying for or committing to a permanent position. Those serving in temporary details are often given more support as colleagues and supervisors understand that the role was accepted on short notice with little time to prepare. Other benefits include expanding professional contacts, gaining perspective on a different part of the VHA, and working on skills, such as flexibility, time management, and perseverance. By succeeding in a detail, employees build professional acumen. After taking on additional challenges they become more competitive for future jobs. The VHA Executive Candidate Development Program requires a 120-day detail, serving as either assistant or associate director, chief of staff, or associate director for patient care services/nurse executive as part of the program.1

 

 

Temporarily leaving a service line to detail in a different service line has an impact on the home service because of the restrictions imposed. These restrictions guarantee that the employee can return to the original position at the end of a detail, thus providing a sense of job security; however, the home service line is down an employee.

Given these considerations, the following are key points to establish before undertaking the detail: (1) length of assignment; (2) once started, potential for the assignment to be extended; (3) will the employee be doing any of their prior job or just the new job or a blend of both; (4) possible changes in hours and site of work of the employee; (5) who will supervise the employee; (6) who will write the employee’s review; (7) training or skills needed prior to starting; (8) necessary paperwork; (9) how will the new assignment be communicated to others; (10) what happens if the detail ends sooner than planned; and (11) approval and support of all involved parties.

The employee’s home service may need a temporary plan to cover the employee’s workload, especially if the employee will be detailed to a different service line. The temporary plan may require creativity and flexibility and can be a way to trial the contingency plans for staffing the home service. One benefit to the home service is that the employee will have additional skills on returning that may benefit the home service, and the service will gain a potential leader.

When an employee goes to a different service, that service gains an employee who may bring a new perspective to help solve existing conflicts or problems. This can serve as a time to reset expectations or set new goals prior to the arrival of new leadership. If the detail is a good fit, then there is the chance that the employee may return in the future or refer others to it as a professional opportunity.

Conclusions

A detail can benefit the employee and the home and host services if planned in advance, and all parties support the process. A short-term leadership or administrative assignment can help an employee gain valuable experience for the future.

References

1. US Department of Veterans Affairs. Improve VA’s employee experience.obamaadministration.archives.performance.gov/node/65741.html. Published 2017. Accessed October 19, 2020.

References

1. US Department of Veterans Affairs. Improve VA’s employee experience.obamaadministration.archives.performance.gov/node/65741.html. Published 2017. Accessed October 19, 2020.

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Information blocking: Adolescent confidentiality is collateral damage

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On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Margaret Thew


Unfortunately, the rules do not take into consideration adolescent confidential care. There are eight rules for the exception of releasing information, but it may be a stretch to place adolescent confidential progress notes under any of these eight exceptions. These exceptions are ambiguous and open to interpretation yet require specific documentation as to the limitation of access. Exceptions are prevention of harm; privacy conflicts; the security of the electronic health information; infeasibility, which includes challenges limiting the ability to comply; Health IT performance; content and manner; fees; and licensing.
 

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

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On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Margaret Thew


Unfortunately, the rules do not take into consideration adolescent confidential care. There are eight rules for the exception of releasing information, but it may be a stretch to place adolescent confidential progress notes under any of these eight exceptions. These exceptions are ambiguous and open to interpretation yet require specific documentation as to the limitation of access. Exceptions are prevention of harm; privacy conflicts; the security of the electronic health information; infeasibility, which includes challenges limiting the ability to comply; Health IT performance; content and manner; fees; and licensing.
 

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Margaret Thew


Unfortunately, the rules do not take into consideration adolescent confidential care. There are eight rules for the exception of releasing information, but it may be a stretch to place adolescent confidential progress notes under any of these eight exceptions. These exceptions are ambiguous and open to interpretation yet require specific documentation as to the limitation of access. Exceptions are prevention of harm; privacy conflicts; the security of the electronic health information; infeasibility, which includes challenges limiting the ability to comply; Health IT performance; content and manner; fees; and licensing.
 

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

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Biologics in Pediatric Psoriasis and Atopic Dermatitis: Revolutionizing the Treatment Landscape

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Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.1 Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/TH17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.2 Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.3 A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.4

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (TH17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.7 Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with TH17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.8 The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,9 claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.10 Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting TH2-driven inflammation.11 Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.12 Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

 

 

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block TH2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.13



The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly TH2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.14

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.2 No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.20 Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.25 This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and TH17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

References
  1. Na CH, Chung J, Simpson EL. Quality of life and disease impact of atopic dermatitis and psoriasis on children and their families. Children (Basel). 2019;6:133.
  2. Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. 2020;82:161-201.
  3. Papp K, Thaci D, Marcoux D, et al. Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial. Lancet. 2017;390:40-49.
  4. Bronckers I, Paller AS, West DP, et al. A comparison of psoriasis severity in pediatric patients treated with methotrexate vs biologic agents. JAMA Dermatol. 2020;156:384-392.
  5. Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73:594-603.
  6. Philipp S, Menter A, Nikkels AF, et al. Ustekinumab for the treatmentof moderate-to-severe plaque psoriasis in paediatric patients (>/= 6 to < 12 years of age): efficacy, safety, pharmacokinetic and biomarker results from the open-label CADMUS Jr study. Br J Dermatol. 2020;183:664-672.
  7. Paller AS, Seyger MMB, Alejandro Magarinos G, et al. Efficacy and safety of ixekizumab in a phase III, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS). Br J Dermatol. 2020;183:231-241.
  8. Bruins FM, Bronckers I, Groenewoud HMM, et al. Association between quality of life and improvement in psoriasis severity and extent in pediatric patients. JAMA Dermatol. 2020;156:72-78.
  9. Totri CR, Eichenfield LF, Logan K, et al. Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: the PeDRA TREAT survey. J Am Acad Dermatol. 2017;76:281-285.
  10. Paller AS, Siegfried EC, Vekeman F, et al. Treatment patterns of pediatric patients with atopic dermatitis: a claims data analysis. J Am Acad Dermatol. 2020;82:651-660.
  11. Tsianakas A, Ständer S. Dupilumab: a milestone in the treatment of atopic dermatitis. The Lancet. 2016;10013:4-5.
  12. Simpson EL, Paller AS, Siegfried EC, et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis: a phase 3 randomized clinical trial. JAMA Dermatol. 2020;156:44-56.
  13. Paller AS, Siegfried EC, Thaci D, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol. 2020;83:1282-1293.
  14. Bagci IS, Ruzicka T. IL-31: a new key player in dermatology and beyond. J Allergy Clin Immunol. 2018;141:858-866.
  15. Schwartz G, Paller AS. Targeted therapies for pediatric psoriasis. Semin Cutan Med Surg. 2018;37:167-172.
  16. Dommasch ED, Kim SC, Lee MP, et al. Risk of serious infection in patients receiving systemic medications for the treatment of psoriasis. JAMA Dermatol. 2019;155:1142-1152.
  17. Reich K, Blauvelt A, Armstrong A, et al. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2017;176:752-758.
  18. Bagel J, Lebwohl M, Israel RJ, et al. Immunogenicity and skin clearance recapture in clinical studies of brodalumab. J Am Acad Dermatol. 2020;82:344-351.
  19. Zhu Y, Marini JC, Song M, et al. Immunogenicity of guselkumab is not clinically relevant in patients with moderate-to-severe plaque psoriasis. J Invest Dermatol. 2019;139:1830.e6-1834.e6.
  20. Langley RG, Kasichayanula S, Trivedi M, et al. Pharmacokinetics, immunogenicity, and efficacy of etanercept in pediatric patients with moderate to severe plaque psoriasis. J Clin Pharmacol. 2018;58:340-346.
  21. Paller AS, Siegfried EC, Pariser DM, et al. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol. 2016;74:280-287.e1-3.
  22. Papp K, Gottlieb AB, Naldi L, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015;14:706-714.
  23. Targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: effectiveness and value. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2017/11/ICER_Psoriasis_Update_Draft_Report_04272018.pdf. Published December 2, 2016. Accessed October 26, 2020.
  24. Dupilumab and crisaborole for atopic dermatitis: effectiveness and value. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2016/10/MWCEPAC_ATOPIC_EVIDENCE_REPORT_051217.pdf. Published May 12, 2017. Accessed October 26, 2020.
  25. Siegfried EC, Igelman S, Jaworski JC, et al. Use of dupilumab in pediatric atopic dermatitis: access, dosing, and implications for managing severe atopic dermatitis. Pediatr Dermatol. 2019;36:172-176.
  26. Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008;358:241-251.
  27. Reich A. Secukinumab is highly efficacious and has a favorable safety profile in pediatric patients with moderate-to-severe plaque psoriasis. Presented at: AAD Virtual Meeting Experience; June 12–14, 2020.
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Author and Disclosure Information

From the Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Dr. Paller also is from the Department of Pediatrics.

Dr. Scott reports no conflict of interest. Dr. Paller has been an investigator and/or consultant for AbbVie Inc; Abeona Therapeutics; Almirall; AnaptysBio; Asana; Boehringer Ingelheim; BridgeBio Pharma; Dermavant Sciences Ltd; Dermira, Inc; Eli Lilly and Company; Exicure; Forte Biosciences Inc; Galderma Laboratories, LP; Incyte Corporation; Janssen Pharmaceuticals, Inc; LEO Pharma; Lifemax Laboratories, Inc; Novartis; Pfizer; RAPT Therapeutics, Inc; Regeneron Pharmaceuticals; Sanofi Genzyme; Sol-Gel Technologies Ltd; and UCB.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Amy S. Paller, MD, Department of Dermatology, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (apaller@northwestern.edu).

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Author and Disclosure Information

From the Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Dr. Paller also is from the Department of Pediatrics.

Dr. Scott reports no conflict of interest. Dr. Paller has been an investigator and/or consultant for AbbVie Inc; Abeona Therapeutics; Almirall; AnaptysBio; Asana; Boehringer Ingelheim; BridgeBio Pharma; Dermavant Sciences Ltd; Dermira, Inc; Eli Lilly and Company; Exicure; Forte Biosciences Inc; Galderma Laboratories, LP; Incyte Corporation; Janssen Pharmaceuticals, Inc; LEO Pharma; Lifemax Laboratories, Inc; Novartis; Pfizer; RAPT Therapeutics, Inc; Regeneron Pharmaceuticals; Sanofi Genzyme; Sol-Gel Technologies Ltd; and UCB.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Amy S. Paller, MD, Department of Dermatology, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (apaller@northwestern.edu).

Author and Disclosure Information

From the Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Dr. Paller also is from the Department of Pediatrics.

Dr. Scott reports no conflict of interest. Dr. Paller has been an investigator and/or consultant for AbbVie Inc; Abeona Therapeutics; Almirall; AnaptysBio; Asana; Boehringer Ingelheim; BridgeBio Pharma; Dermavant Sciences Ltd; Dermira, Inc; Eli Lilly and Company; Exicure; Forte Biosciences Inc; Galderma Laboratories, LP; Incyte Corporation; Janssen Pharmaceuticals, Inc; LEO Pharma; Lifemax Laboratories, Inc; Novartis; Pfizer; RAPT Therapeutics, Inc; Regeneron Pharmaceuticals; Sanofi Genzyme; Sol-Gel Technologies Ltd; and UCB.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Amy S. Paller, MD, Department of Dermatology, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (apaller@northwestern.edu).

Article PDF
Article PDF

 

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.1 Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/TH17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.2 Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.3 A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.4

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (TH17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.7 Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with TH17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.8 The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,9 claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.10 Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting TH2-driven inflammation.11 Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.12 Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

 

 

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block TH2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.13



The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly TH2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.14

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.2 No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.20 Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.25 This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and TH17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

 

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.1 Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/TH17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.2 Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.3 A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.4

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (TH17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.7 Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with TH17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.8 The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,9 claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.10 Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting TH2-driven inflammation.11 Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.12 Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

 

 

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block TH2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.13



The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly TH2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.14

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.2 No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.20 Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.25 This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and TH17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

References
  1. Na CH, Chung J, Simpson EL. Quality of life and disease impact of atopic dermatitis and psoriasis on children and their families. Children (Basel). 2019;6:133.
  2. Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. 2020;82:161-201.
  3. Papp K, Thaci D, Marcoux D, et al. Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial. Lancet. 2017;390:40-49.
  4. Bronckers I, Paller AS, West DP, et al. A comparison of psoriasis severity in pediatric patients treated with methotrexate vs biologic agents. JAMA Dermatol. 2020;156:384-392.
  5. Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73:594-603.
  6. Philipp S, Menter A, Nikkels AF, et al. Ustekinumab for the treatmentof moderate-to-severe plaque psoriasis in paediatric patients (>/= 6 to < 12 years of age): efficacy, safety, pharmacokinetic and biomarker results from the open-label CADMUS Jr study. Br J Dermatol. 2020;183:664-672.
  7. Paller AS, Seyger MMB, Alejandro Magarinos G, et al. Efficacy and safety of ixekizumab in a phase III, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS). Br J Dermatol. 2020;183:231-241.
  8. Bruins FM, Bronckers I, Groenewoud HMM, et al. Association between quality of life and improvement in psoriasis severity and extent in pediatric patients. JAMA Dermatol. 2020;156:72-78.
  9. Totri CR, Eichenfield LF, Logan K, et al. Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: the PeDRA TREAT survey. J Am Acad Dermatol. 2017;76:281-285.
  10. Paller AS, Siegfried EC, Vekeman F, et al. Treatment patterns of pediatric patients with atopic dermatitis: a claims data analysis. J Am Acad Dermatol. 2020;82:651-660.
  11. Tsianakas A, Ständer S. Dupilumab: a milestone in the treatment of atopic dermatitis. The Lancet. 2016;10013:4-5.
  12. Simpson EL, Paller AS, Siegfried EC, et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis: a phase 3 randomized clinical trial. JAMA Dermatol. 2020;156:44-56.
  13. Paller AS, Siegfried EC, Thaci D, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol. 2020;83:1282-1293.
  14. Bagci IS, Ruzicka T. IL-31: a new key player in dermatology and beyond. J Allergy Clin Immunol. 2018;141:858-866.
  15. Schwartz G, Paller AS. Targeted therapies for pediatric psoriasis. Semin Cutan Med Surg. 2018;37:167-172.
  16. Dommasch ED, Kim SC, Lee MP, et al. Risk of serious infection in patients receiving systemic medications for the treatment of psoriasis. JAMA Dermatol. 2019;155:1142-1152.
  17. Reich K, Blauvelt A, Armstrong A, et al. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2017;176:752-758.
  18. Bagel J, Lebwohl M, Israel RJ, et al. Immunogenicity and skin clearance recapture in clinical studies of brodalumab. J Am Acad Dermatol. 2020;82:344-351.
  19. Zhu Y, Marini JC, Song M, et al. Immunogenicity of guselkumab is not clinically relevant in patients with moderate-to-severe plaque psoriasis. J Invest Dermatol. 2019;139:1830.e6-1834.e6.
  20. Langley RG, Kasichayanula S, Trivedi M, et al. Pharmacokinetics, immunogenicity, and efficacy of etanercept in pediatric patients with moderate to severe plaque psoriasis. J Clin Pharmacol. 2018;58:340-346.
  21. Paller AS, Siegfried EC, Pariser DM, et al. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol. 2016;74:280-287.e1-3.
  22. Papp K, Gottlieb AB, Naldi L, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015;14:706-714.
  23. Targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: effectiveness and value. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2017/11/ICER_Psoriasis_Update_Draft_Report_04272018.pdf. Published December 2, 2016. Accessed October 26, 2020.
  24. Dupilumab and crisaborole for atopic dermatitis: effectiveness and value. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2016/10/MWCEPAC_ATOPIC_EVIDENCE_REPORT_051217.pdf. Published May 12, 2017. Accessed October 26, 2020.
  25. Siegfried EC, Igelman S, Jaworski JC, et al. Use of dupilumab in pediatric atopic dermatitis: access, dosing, and implications for managing severe atopic dermatitis. Pediatr Dermatol. 2019;36:172-176.
  26. Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008;358:241-251.
  27. Reich A. Secukinumab is highly efficacious and has a favorable safety profile in pediatric patients with moderate-to-severe plaque psoriasis. Presented at: AAD Virtual Meeting Experience; June 12–14, 2020.
References
  1. Na CH, Chung J, Simpson EL. Quality of life and disease impact of atopic dermatitis and psoriasis on children and their families. Children (Basel). 2019;6:133.
  2. Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. 2020;82:161-201.
  3. Papp K, Thaci D, Marcoux D, et al. Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial. Lancet. 2017;390:40-49.
  4. Bronckers I, Paller AS, West DP, et al. A comparison of psoriasis severity in pediatric patients treated with methotrexate vs biologic agents. JAMA Dermatol. 2020;156:384-392.
  5. Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73:594-603.
  6. Philipp S, Menter A, Nikkels AF, et al. Ustekinumab for the treatmentof moderate-to-severe plaque psoriasis in paediatric patients (>/= 6 to < 12 years of age): efficacy, safety, pharmacokinetic and biomarker results from the open-label CADMUS Jr study. Br J Dermatol. 2020;183:664-672.
  7. Paller AS, Seyger MMB, Alejandro Magarinos G, et al. Efficacy and safety of ixekizumab in a phase III, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS). Br J Dermatol. 2020;183:231-241.
  8. Bruins FM, Bronckers I, Groenewoud HMM, et al. Association between quality of life and improvement in psoriasis severity and extent in pediatric patients. JAMA Dermatol. 2020;156:72-78.
  9. Totri CR, Eichenfield LF, Logan K, et al. Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: the PeDRA TREAT survey. J Am Acad Dermatol. 2017;76:281-285.
  10. Paller AS, Siegfried EC, Vekeman F, et al. Treatment patterns of pediatric patients with atopic dermatitis: a claims data analysis. J Am Acad Dermatol. 2020;82:651-660.
  11. Tsianakas A, Ständer S. Dupilumab: a milestone in the treatment of atopic dermatitis. The Lancet. 2016;10013:4-5.
  12. Simpson EL, Paller AS, Siegfried EC, et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis: a phase 3 randomized clinical trial. JAMA Dermatol. 2020;156:44-56.
  13. Paller AS, Siegfried EC, Thaci D, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol. 2020;83:1282-1293.
  14. Bagci IS, Ruzicka T. IL-31: a new key player in dermatology and beyond. J Allergy Clin Immunol. 2018;141:858-866.
  15. Schwartz G, Paller AS. Targeted therapies for pediatric psoriasis. Semin Cutan Med Surg. 2018;37:167-172.
  16. Dommasch ED, Kim SC, Lee MP, et al. Risk of serious infection in patients receiving systemic medications for the treatment of psoriasis. JAMA Dermatol. 2019;155:1142-1152.
  17. Reich K, Blauvelt A, Armstrong A, et al. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2017;176:752-758.
  18. Bagel J, Lebwohl M, Israel RJ, et al. Immunogenicity and skin clearance recapture in clinical studies of brodalumab. J Am Acad Dermatol. 2020;82:344-351.
  19. Zhu Y, Marini JC, Song M, et al. Immunogenicity of guselkumab is not clinically relevant in patients with moderate-to-severe plaque psoriasis. J Invest Dermatol. 2019;139:1830.e6-1834.e6.
  20. Langley RG, Kasichayanula S, Trivedi M, et al. Pharmacokinetics, immunogenicity, and efficacy of etanercept in pediatric patients with moderate to severe plaque psoriasis. J Clin Pharmacol. 2018;58:340-346.
  21. Paller AS, Siegfried EC, Pariser DM, et al. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol. 2016;74:280-287.e1-3.
  22. Papp K, Gottlieb AB, Naldi L, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015;14:706-714.
  23. Targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: effectiveness and value. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2017/11/ICER_Psoriasis_Update_Draft_Report_04272018.pdf. Published December 2, 2016. Accessed October 26, 2020.
  24. Dupilumab and crisaborole for atopic dermatitis: effectiveness and value. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2016/10/MWCEPAC_ATOPIC_EVIDENCE_REPORT_051217.pdf. Published May 12, 2017. Accessed October 26, 2020.
  25. Siegfried EC, Igelman S, Jaworski JC, et al. Use of dupilumab in pediatric atopic dermatitis: access, dosing, and implications for managing severe atopic dermatitis. Pediatr Dermatol. 2019;36:172-176.
  26. Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008;358:241-251.
  27. Reich A. Secukinumab is highly efficacious and has a favorable safety profile in pediatric patients with moderate-to-severe plaque psoriasis. Presented at: AAD Virtual Meeting Experience; June 12–14, 2020.
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Dermatologists as Social Media Contributors During the COVID-19 Pandemic

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On December 31, 2019, cases of a severe pneumonia in patients in Wuhan, Hubei Province, China, were reported to the World Health Organization.1,2 The novel coronavirus—severe acute respiratory syndrome coronavirus 2—was identified, and the coronavirus disease 2019 (COVID-19) became a public health emergency of international concern.1 In March 2020, the World Health Organization officially characterized COVID-19 as a pandemic.3 As of October 2020, more than 42.3 million cases and 1.1 million deaths from COVID-19 have been confirmed worldwide.4

As more understanding of severe acute respiratory syndrome coronavirus 2 develops, various cutaneous manifestations of COVID-19 are being uncovered.5 The most common cutaneous manifestations of COVID-19 reported in the literature are maculopapular or morbilliform exanthem (36.1% of cutaneous manifestations), papulovesicular rash (34.7%), painful acral red purple papules (15.3%), urticaria (9.7%), livedo reticularis lesions (2.8%), and petechiae (1.4%).5

Interestingly, a series of unique cases was identified in April 2020 by a group of dermatologists in Spain. Most patients were children (median age, 13 years) or young adults (median age, 31 years; average age, 36 years; adult age range, 18–91 years).1 Reporting on a representative sample of 6 patients in that series, the group noted that lesions, initially reddish, papular, and resembling chilblains (pernio), progressively became purpuric and flattened in the course of 1 week. Although the lesions presented with some referred discomfort or pain with palpation, they were not highly symptomatic, and no signs of ischemia or Raynaud syndrome were identified. Over time, lesions self-resolved without intervention. Most patients also did not present with what are considered classic COVID-19 signs or symptoms. Only the oldest patient (aged 91 years) presented with a notable respiratory condition; the remaining patients generally were in good health.1 Dermatologists in Italy, France, and the United States also have witnessed these COVID-19–associated cutaneous manifestations.

Scientific understanding of COVID-19 and its associated dermatologic symptoms is evolving. Attention has turned to social media to inform and provide possible health solutions during this unprecedented medical crisis.6 Strict physical distancing measures have made patients and providers alike reliant on global digital social networks, such as Instagram, Twitter, and Facebook, to facilitate information sharing about COVID-19.7 The abundance of nonexpert advice and misinformation on social media makes communication of unbiased expert information difficult.8,9 Furthermore, there is a need for dermatologists to provide medical information to patients regarding COVID-19, such as dermatologic manifestations, and clear guidance on immunobiologic or systemic medications during this unprecedented time.9

In recent years, dermatologists have established a growing presence on social media, with many recognized as social media influencers with the ability to affect patients’ health-related behavior.10 Social media frequently has been used by patients to solicit advice regarding skin concerns.9,10 Many individuals, in fact, never see a physician after consulting social media for medical concerns or professional advice.9

In addition, as of March 2020, more than 61% of health care workers were found to use social media as a source of COVID-19–related information.11 Therefore, dermatologists should utilize social media as a platform to share evidence-based information with the public and other health care workers.

Through social media, dermatologists can post high-quality images with clear descriptions to fully characterize skin manifestations in patients with COVID-19. The process of capturing and posting images to the virtual world using a smartphone allows practitioners to gain advice from peers and consultants, share findings with colleagues, and inform the public.12 Social media posts of many deidentified clinical images of rashes in COVID-19–infected patients already have enabled rapid recognition of skin signs by dermatologists.13

Social media sites also are resources where organizations can post updated, evidence-based findings from academic journals. For example, the American Academy of Dermatology and its official journal, the Journal of the American Academy of Dermatology, had more than 22,000 and 27,000 Instagram followers, respectively, as of a March 2020 analysis.14 Recent online forums and social media posts contain accessible, graphical, patient-friendly images and information on evidence-based treatments for skin disease during the COVID-19 pandemic.13



We should consider initiatives that empower dermatologists to use social media to post unbiased, evidence-based information regarding manifestations of COVID-19 and guidelines for treatment of skin disease during this medical crisis. We hope that dermatologists will help lead the global response to the COVID-19 pandemic and contribute to the evolving knowledge base by characterizing COVID-19–related rashes, understanding their implications, and determining the best evidence for treatment.

References
  1. Landa N, Mendieta-Eckert M, Fonda-Pascual P, et al. Chilblain-like lesions on feet and hands during the COVID-19 pandemic. Int J Dermatol. 2020;59:739-743.
  2. Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance. JAMA. 2020;323:709-710.
  3. World Health Organization. Coronavirus disease (COVID-19) Situation Report – 133. WHO Website. June 1, 2020. www.who.int/docs/default-source/coronaviruse/situation-reports/20200601-covid-19-sitrep-133.pdf?sfvrsn=9a56f2ac_4. Accessed October 14, 2020.
  4. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at John Hopkins University. John Hopkins Coronavirus Resource Center website. https://coronavirus.jhu.edu/map.html. Accessed October 24, 2020.
  5. Sachdeva M, Gianotti R, Shah M, et al. Cutaneous manifestations of COVID-19: report of three cases and a review of literature. J Dermatolog Sci. 2020;98:75-81.
  6. Kapoor A, Guha S, Kanti Das M, et al. Digital healthcare: the only solution for better healthcare during COVID-19 pandemic? Indian Heart J. 2020;72:61-64.
  7. Limaye RJ, Sauer M, Ali J, et al. Building trust while influencing online COVID-19 content in the social media world. Lancet Digit Health. 2020;2:E277-E278.
  8. Chawla S. COVID-19: challenges and opportunities for dermatology response. J Dermatolog Treat. 2020;31:326-326.
  9. Schoenberg E, Shalabi D, Wang JV, et al. Public social media consultations for dermatologic conditions: an online survey. Dermatol Online J. 2020;26:6.
  10. DeBord LC, Patel V, Braun TL, et al. Social media in dermatology: clinical relevance, academic value, and trends across platforms. J Dermatolog Treat. 2019;30:511-518.
  11. Bhagavathula AS, Aldhaleei WA, Rahmani J, et al. Knowledge and perceptions of COVID-19 among health care workers: cross-sectional study. JMIR Public Health Surveill. 2020;6:E19160.
  12. Ashique KT, Kaliyadan F, Aurangabadkar SJ. Clinical photography in dermatology using smartphones: an overview. Indian Dermatol Online J. 2015;6:158-163.
  13. Madigan LM, Micheletti RG, Shinkai K. How dermatologists can learn and contribute at the leading edge of the COVID-19 global pandemic. JAMA Dermatol. 2020;156:733-734.
  14. Guzman AK, Barbieri JS. Response to: “Dermatologists in social media: a study on top influencers, posts, and user engagement” [published online April 20, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.03.118.
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Dr. Uppal is from Albany Medical College, New York. Mr. Kearns is from Loma Linda School of Medicine, California. Ms. Chat is from the Medical College of Georgia at Augusta University. Dr. Wu is from the Research and Education Foundation, Irvine, California.

The authors report no conflict of interest.

Correspondence: Jashin J. Wu, MD (jashinwu@gmail.com).

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Dr. Uppal is from Albany Medical College, New York. Mr. Kearns is from Loma Linda School of Medicine, California. Ms. Chat is from the Medical College of Georgia at Augusta University. Dr. Wu is from the Research and Education Foundation, Irvine, California.

The authors report no conflict of interest.

Correspondence: Jashin J. Wu, MD (jashinwu@gmail.com).

Author and Disclosure Information

Dr. Uppal is from Albany Medical College, New York. Mr. Kearns is from Loma Linda School of Medicine, California. Ms. Chat is from the Medical College of Georgia at Augusta University. Dr. Wu is from the Research and Education Foundation, Irvine, California.

The authors report no conflict of interest.

Correspondence: Jashin J. Wu, MD (jashinwu@gmail.com).

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On December 31, 2019, cases of a severe pneumonia in patients in Wuhan, Hubei Province, China, were reported to the World Health Organization.1,2 The novel coronavirus—severe acute respiratory syndrome coronavirus 2—was identified, and the coronavirus disease 2019 (COVID-19) became a public health emergency of international concern.1 In March 2020, the World Health Organization officially characterized COVID-19 as a pandemic.3 As of October 2020, more than 42.3 million cases and 1.1 million deaths from COVID-19 have been confirmed worldwide.4

As more understanding of severe acute respiratory syndrome coronavirus 2 develops, various cutaneous manifestations of COVID-19 are being uncovered.5 The most common cutaneous manifestations of COVID-19 reported in the literature are maculopapular or morbilliform exanthem (36.1% of cutaneous manifestations), papulovesicular rash (34.7%), painful acral red purple papules (15.3%), urticaria (9.7%), livedo reticularis lesions (2.8%), and petechiae (1.4%).5

Interestingly, a series of unique cases was identified in April 2020 by a group of dermatologists in Spain. Most patients were children (median age, 13 years) or young adults (median age, 31 years; average age, 36 years; adult age range, 18–91 years).1 Reporting on a representative sample of 6 patients in that series, the group noted that lesions, initially reddish, papular, and resembling chilblains (pernio), progressively became purpuric and flattened in the course of 1 week. Although the lesions presented with some referred discomfort or pain with palpation, they were not highly symptomatic, and no signs of ischemia or Raynaud syndrome were identified. Over time, lesions self-resolved without intervention. Most patients also did not present with what are considered classic COVID-19 signs or symptoms. Only the oldest patient (aged 91 years) presented with a notable respiratory condition; the remaining patients generally were in good health.1 Dermatologists in Italy, France, and the United States also have witnessed these COVID-19–associated cutaneous manifestations.

Scientific understanding of COVID-19 and its associated dermatologic symptoms is evolving. Attention has turned to social media to inform and provide possible health solutions during this unprecedented medical crisis.6 Strict physical distancing measures have made patients and providers alike reliant on global digital social networks, such as Instagram, Twitter, and Facebook, to facilitate information sharing about COVID-19.7 The abundance of nonexpert advice and misinformation on social media makes communication of unbiased expert information difficult.8,9 Furthermore, there is a need for dermatologists to provide medical information to patients regarding COVID-19, such as dermatologic manifestations, and clear guidance on immunobiologic or systemic medications during this unprecedented time.9

In recent years, dermatologists have established a growing presence on social media, with many recognized as social media influencers with the ability to affect patients’ health-related behavior.10 Social media frequently has been used by patients to solicit advice regarding skin concerns.9,10 Many individuals, in fact, never see a physician after consulting social media for medical concerns or professional advice.9

In addition, as of March 2020, more than 61% of health care workers were found to use social media as a source of COVID-19–related information.11 Therefore, dermatologists should utilize social media as a platform to share evidence-based information with the public and other health care workers.

Through social media, dermatologists can post high-quality images with clear descriptions to fully characterize skin manifestations in patients with COVID-19. The process of capturing and posting images to the virtual world using a smartphone allows practitioners to gain advice from peers and consultants, share findings with colleagues, and inform the public.12 Social media posts of many deidentified clinical images of rashes in COVID-19–infected patients already have enabled rapid recognition of skin signs by dermatologists.13

Social media sites also are resources where organizations can post updated, evidence-based findings from academic journals. For example, the American Academy of Dermatology and its official journal, the Journal of the American Academy of Dermatology, had more than 22,000 and 27,000 Instagram followers, respectively, as of a March 2020 analysis.14 Recent online forums and social media posts contain accessible, graphical, patient-friendly images and information on evidence-based treatments for skin disease during the COVID-19 pandemic.13



We should consider initiatives that empower dermatologists to use social media to post unbiased, evidence-based information regarding manifestations of COVID-19 and guidelines for treatment of skin disease during this medical crisis. We hope that dermatologists will help lead the global response to the COVID-19 pandemic and contribute to the evolving knowledge base by characterizing COVID-19–related rashes, understanding their implications, and determining the best evidence for treatment.

On December 31, 2019, cases of a severe pneumonia in patients in Wuhan, Hubei Province, China, were reported to the World Health Organization.1,2 The novel coronavirus—severe acute respiratory syndrome coronavirus 2—was identified, and the coronavirus disease 2019 (COVID-19) became a public health emergency of international concern.1 In March 2020, the World Health Organization officially characterized COVID-19 as a pandemic.3 As of October 2020, more than 42.3 million cases and 1.1 million deaths from COVID-19 have been confirmed worldwide.4

As more understanding of severe acute respiratory syndrome coronavirus 2 develops, various cutaneous manifestations of COVID-19 are being uncovered.5 The most common cutaneous manifestations of COVID-19 reported in the literature are maculopapular or morbilliform exanthem (36.1% of cutaneous manifestations), papulovesicular rash (34.7%), painful acral red purple papules (15.3%), urticaria (9.7%), livedo reticularis lesions (2.8%), and petechiae (1.4%).5

Interestingly, a series of unique cases was identified in April 2020 by a group of dermatologists in Spain. Most patients were children (median age, 13 years) or young adults (median age, 31 years; average age, 36 years; adult age range, 18–91 years).1 Reporting on a representative sample of 6 patients in that series, the group noted that lesions, initially reddish, papular, and resembling chilblains (pernio), progressively became purpuric and flattened in the course of 1 week. Although the lesions presented with some referred discomfort or pain with palpation, they were not highly symptomatic, and no signs of ischemia or Raynaud syndrome were identified. Over time, lesions self-resolved without intervention. Most patients also did not present with what are considered classic COVID-19 signs or symptoms. Only the oldest patient (aged 91 years) presented with a notable respiratory condition; the remaining patients generally were in good health.1 Dermatologists in Italy, France, and the United States also have witnessed these COVID-19–associated cutaneous manifestations.

Scientific understanding of COVID-19 and its associated dermatologic symptoms is evolving. Attention has turned to social media to inform and provide possible health solutions during this unprecedented medical crisis.6 Strict physical distancing measures have made patients and providers alike reliant on global digital social networks, such as Instagram, Twitter, and Facebook, to facilitate information sharing about COVID-19.7 The abundance of nonexpert advice and misinformation on social media makes communication of unbiased expert information difficult.8,9 Furthermore, there is a need for dermatologists to provide medical information to patients regarding COVID-19, such as dermatologic manifestations, and clear guidance on immunobiologic or systemic medications during this unprecedented time.9

In recent years, dermatologists have established a growing presence on social media, with many recognized as social media influencers with the ability to affect patients’ health-related behavior.10 Social media frequently has been used by patients to solicit advice regarding skin concerns.9,10 Many individuals, in fact, never see a physician after consulting social media for medical concerns or professional advice.9

In addition, as of March 2020, more than 61% of health care workers were found to use social media as a source of COVID-19–related information.11 Therefore, dermatologists should utilize social media as a platform to share evidence-based information with the public and other health care workers.

Through social media, dermatologists can post high-quality images with clear descriptions to fully characterize skin manifestations in patients with COVID-19. The process of capturing and posting images to the virtual world using a smartphone allows practitioners to gain advice from peers and consultants, share findings with colleagues, and inform the public.12 Social media posts of many deidentified clinical images of rashes in COVID-19–infected patients already have enabled rapid recognition of skin signs by dermatologists.13

Social media sites also are resources where organizations can post updated, evidence-based findings from academic journals. For example, the American Academy of Dermatology and its official journal, the Journal of the American Academy of Dermatology, had more than 22,000 and 27,000 Instagram followers, respectively, as of a March 2020 analysis.14 Recent online forums and social media posts contain accessible, graphical, patient-friendly images and information on evidence-based treatments for skin disease during the COVID-19 pandemic.13



We should consider initiatives that empower dermatologists to use social media to post unbiased, evidence-based information regarding manifestations of COVID-19 and guidelines for treatment of skin disease during this medical crisis. We hope that dermatologists will help lead the global response to the COVID-19 pandemic and contribute to the evolving knowledge base by characterizing COVID-19–related rashes, understanding their implications, and determining the best evidence for treatment.

References
  1. Landa N, Mendieta-Eckert M, Fonda-Pascual P, et al. Chilblain-like lesions on feet and hands during the COVID-19 pandemic. Int J Dermatol. 2020;59:739-743.
  2. Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance. JAMA. 2020;323:709-710.
  3. World Health Organization. Coronavirus disease (COVID-19) Situation Report – 133. WHO Website. June 1, 2020. www.who.int/docs/default-source/coronaviruse/situation-reports/20200601-covid-19-sitrep-133.pdf?sfvrsn=9a56f2ac_4. Accessed October 14, 2020.
  4. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at John Hopkins University. John Hopkins Coronavirus Resource Center website. https://coronavirus.jhu.edu/map.html. Accessed October 24, 2020.
  5. Sachdeva M, Gianotti R, Shah M, et al. Cutaneous manifestations of COVID-19: report of three cases and a review of literature. J Dermatolog Sci. 2020;98:75-81.
  6. Kapoor A, Guha S, Kanti Das M, et al. Digital healthcare: the only solution for better healthcare during COVID-19 pandemic? Indian Heart J. 2020;72:61-64.
  7. Limaye RJ, Sauer M, Ali J, et al. Building trust while influencing online COVID-19 content in the social media world. Lancet Digit Health. 2020;2:E277-E278.
  8. Chawla S. COVID-19: challenges and opportunities for dermatology response. J Dermatolog Treat. 2020;31:326-326.
  9. Schoenberg E, Shalabi D, Wang JV, et al. Public social media consultations for dermatologic conditions: an online survey. Dermatol Online J. 2020;26:6.
  10. DeBord LC, Patel V, Braun TL, et al. Social media in dermatology: clinical relevance, academic value, and trends across platforms. J Dermatolog Treat. 2019;30:511-518.
  11. Bhagavathula AS, Aldhaleei WA, Rahmani J, et al. Knowledge and perceptions of COVID-19 among health care workers: cross-sectional study. JMIR Public Health Surveill. 2020;6:E19160.
  12. Ashique KT, Kaliyadan F, Aurangabadkar SJ. Clinical photography in dermatology using smartphones: an overview. Indian Dermatol Online J. 2015;6:158-163.
  13. Madigan LM, Micheletti RG, Shinkai K. How dermatologists can learn and contribute at the leading edge of the COVID-19 global pandemic. JAMA Dermatol. 2020;156:733-734.
  14. Guzman AK, Barbieri JS. Response to: “Dermatologists in social media: a study on top influencers, posts, and user engagement” [published online April 20, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.03.118.
References
  1. Landa N, Mendieta-Eckert M, Fonda-Pascual P, et al. Chilblain-like lesions on feet and hands during the COVID-19 pandemic. Int J Dermatol. 2020;59:739-743.
  2. Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance. JAMA. 2020;323:709-710.
  3. World Health Organization. Coronavirus disease (COVID-19) Situation Report – 133. WHO Website. June 1, 2020. www.who.int/docs/default-source/coronaviruse/situation-reports/20200601-covid-19-sitrep-133.pdf?sfvrsn=9a56f2ac_4. Accessed October 14, 2020.
  4. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at John Hopkins University. John Hopkins Coronavirus Resource Center website. https://coronavirus.jhu.edu/map.html. Accessed October 24, 2020.
  5. Sachdeva M, Gianotti R, Shah M, et al. Cutaneous manifestations of COVID-19: report of three cases and a review of literature. J Dermatolog Sci. 2020;98:75-81.
  6. Kapoor A, Guha S, Kanti Das M, et al. Digital healthcare: the only solution for better healthcare during COVID-19 pandemic? Indian Heart J. 2020;72:61-64.
  7. Limaye RJ, Sauer M, Ali J, et al. Building trust while influencing online COVID-19 content in the social media world. Lancet Digit Health. 2020;2:E277-E278.
  8. Chawla S. COVID-19: challenges and opportunities for dermatology response. J Dermatolog Treat. 2020;31:326-326.
  9. Schoenberg E, Shalabi D, Wang JV, et al. Public social media consultations for dermatologic conditions: an online survey. Dermatol Online J. 2020;26:6.
  10. DeBord LC, Patel V, Braun TL, et al. Social media in dermatology: clinical relevance, academic value, and trends across platforms. J Dermatolog Treat. 2019;30:511-518.
  11. Bhagavathula AS, Aldhaleei WA, Rahmani J, et al. Knowledge and perceptions of COVID-19 among health care workers: cross-sectional study. JMIR Public Health Surveill. 2020;6:E19160.
  12. Ashique KT, Kaliyadan F, Aurangabadkar SJ. Clinical photography in dermatology using smartphones: an overview. Indian Dermatol Online J. 2015;6:158-163.
  13. Madigan LM, Micheletti RG, Shinkai K. How dermatologists can learn and contribute at the leading edge of the COVID-19 global pandemic. JAMA Dermatol. 2020;156:733-734.
  14. Guzman AK, Barbieri JS. Response to: “Dermatologists in social media: a study on top influencers, posts, and user engagement” [published online April 20, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.03.118.
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  • With the coronavirus disease 2019 (COVID-19) pandemic, strict physical distancing measures have made patients and providers alike reliant on global digital social networks such as Instagram, Twitter, and Facebook to facilitate information sharing about COVID-19.
  • Dermatologists should utilize social media as a platform to post unbiased, evidence-based information regarding manifestations of COVID-19 and guidelines for treatment of skin disease during the global pandemic.
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Maternal oxygen in labor: False reassurance?

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Maternal oxygen in labor:
False reassurance?

 

 

CASE Heart rate tracing suggests fetal distress

Ms. M. presents for elective induction of labor at 39 weeks’ gestation. During the course of her labor, a Category II fetal heart rate (FHR) tracing is noted, and maternal oxygen is administered as part of the intrauterine resuscitative efforts. Her infant ultimately was delivered vaginally with an arterial cord blood pH of 7.1 and Apgar scores of 5 and 7.

Should intrauterine resuscitation include maternal oxygen administration?

It is a common sight on labor and delivery: An FHR monitoring strip is noted to be a Category II tracing. There may be fetal tachycardia, late decelerations, or perhaps decreased variability. The nurse or physician goes to the laboring mother’s room, checks cervical dilation, changes the patient’s position, and puts an oxygen mask over her face.

The American College of Obstetricians and Gynecologists (ACOG) lists maternal oxygen administration, most commonly at 10 L/min via a nonrebreather face mask, as an intrauterine resuscitative measure for Category II or Category III FHR tracings.1 Maternal oxygen is used to treat abnormal FHR tracings in approximately half of all births in the United States.2 Despite these recommendations and the frequency of its use, however, evidence is limited that maternal oxygenation improves neonatal outcome. In fact, there is emerging evidence of potential harm.

Why use oxygen?

The use of maternal oxygen supplementation intuitively makes sense. We know that certain abnormalities in FHR tracings can signal fetal hypoxia. Left untreated, the hypoxia could lead to fetal acidemia and associated neonatal sequelae. Theoretically, the administration of maternal oxygen should lead to improved fetal oxygenation and improved fetal outcome. This is supported by studies from the 1960s that demonstrate improved FHR tracings after maternal oxygen administration.3

This idea was further supported by studies that demonstrated an increase in fetal oxygen levels when maternal oxygen is administered. Haydon and colleagues evaluated the administration of maternal oxygen in women with nonreassuring FHR tracings.4 Their data showed that maternal oxygen administration increased fetal oxygen as measured by fetal pulse oximetry. The lower the initial fetal oxygen levels prior to oxygen administration, the greater the increase.

Despite these findings, evidence for improved neonatal outcomes is lacking.5 While heart rate tracings and fetal oxygen saturation may be improved with maternal oxygen supplementation, neonatal morbidity appears to remain unchanged (FIGURE). In fact, newer research suggests potential harm. Although an improved FHR tracing may be comforting to the clinician, the end result may be less so. Given these findings on maternal oxygen supplementation, it is time to break this practice habit.

Maternal cardiovascular effects

Most of the literature on maternal hyperoxygenation focuses on fetal response. Before examining the effects on the fetus, however, we must consider the effect on the mother. Cardiovascular changes occur during and after maternal oxygen administration that should be taken into account.

McHugh and colleagues measured the hemodynamic changes in 46 pregnant and 20 nonpregnant women before, immediately, and 10 minutes after a 30-minute period of high-flow oxygen administration.6 While there were no changes in the nonpregnant women’s parameters, in the pregnant women heart rate and stroke volume were decreased after oxygen administration. Additionally, systemic vascular resistance increased and did not return to baseline by 10 minutes postadministration.

Since the purpose of the maternal oxygen administration is to increase oxygen to the fetus, this decrease in cardiac output and increase in systemic vascular resistance is concerning. These results may negate the intended effect of increased oxygen delivery to the fetus.

Continue to: Maternal and fetal oxidative stress...

 

 

Maternal and fetal oxidative stress

Assuming that the abnormal FHR tracing in our case patient is actually due to fetal hypoxia, it would seem prudent to increase fetal oxygenation. However, fetal hyperoxygenation may lead to free radical damage that could worsen neonatal outcomes. Oxidative stress, which can be caused by both hypoxia and hyperoxia, can lead to endothelial and cell receptor damage. This is known to contribute to the cerebral damage of hypoxic-ischemic encephalopathy.

In a randomized trial, Khaw and colleagues measured lipid peroxidases as a “free radical footprint” in women undergoing elective cesarean delivery who were administered oxygen or room air.7 Maternal and fetal oxygen levels were higher in the oxygen-supplementation group, but lipid peroxidases also were elevated. This finding suggests that the excess oxygen results in free radical formation and potentially negative effects on the neonate.

Although maternal oxygen supplementation frequently is viewed as harmless, this research shows that free radical damage may occur in the mother as well.

Additional research shows that longer durations of oxygen administration are correlated with worsening neonatal outcomes. In a study of liberal versus indicated oxygen use, the average time was approximately 90 minutes.8 Use for longer than 176 minutes was associated with lower oxygen levels in fetal blood. A proposed mechanism for this response is placental vasoconstriction thought to protect the fetus from free radical damage.

Again, if the goal is to increase oxygenation, prolonged maternal oxygen supplementation appears to produce the opposite effect.

Fetal acidemia and neonatal morbidity

If a fetus with an abnormal FHR tracing is thought to be hypoxic or acidemic, adding the potentially harmful effects of free radicals could worsen this condition. This is exactly what Raghuraman and colleagues demonstrated in a large prospective cohort analysis.9 While there was no difference in neonatal morbidity between those receiving oxygen and those on room air, there was a significant difference among infants with acidemia and hyperoxia. Composite morbidity (mechanical ventilation, hypothermic therapy, meconium aspiration, and death) was significantly increased in neonates with both hyperoxia and acidemia compared with nonacidemic hyperoxic infants.9 This is further supported by reports of an increased need for neonatal resuscitation and a fourfold increase in umbilical cord pH of less than 7.2.10

While intrauterine and extrauterine life certainly differ, these findings align with the pediatric literature that supports neonatal resuscitation with room air rather than 100% oxygen.11 Additionally, the intrauterine environment is relatively hypoxic, which may make free radical damage more severe.

Continue to: Oxygen use during the COVID-19 pandemic...

 

 

Oxygen use during the COVID-19 pandemic

While high-flow oxygen by mask is not considered an aerosol-generating procedure according to the Centers for Disease Control and Prevention, data are limited regarding the cleaning and filtering of oxygen. It is unknown if high-flow oxygen by mask increases the risk of infectious disease transmission to care providers. Therefore, in the midst of the COVID-19 pandemic, ACOG currently recommends against using supplemental oxygen for Category II and Category III tracings, since the benefits are not well established and the possibility of harm to providers may be increased.12 Oxygen supplementation still should be used in mothers with hypoxia.

Other intrauterine resuscitation options

Maternal oxygen administration does not appear beneficial for neonatal outcomes, but other methods can be used. An intravenous fluid bolus and lateral positioning of the mother, for example, are both associated with increased fetal oxygenation. Reducing uterine activity by discontinuing oxytocin or cervical ripening agents or by administering a tocolytic also can improve FHR abnormalities. Oxygen use should be reserved for patients with maternal hypoxia.

The bottom line

The liberal use of maternal oxygenation for the management of abnormal FHR tracings should be stopped. Clear evidence of its benefit is lacking, and the real possibility of fetal and maternal harm remains. This may be especially true during the COVID-19 pandemic. ●

References
  1. American College of Obstetricians and Gynecologists. Practice bulletin No. 116. Management of intrapartum fetal heart rate tracings. Obstet Gynecol. 2010;116:1232-1240. 
  2. Hamel MS, Anderson BL, Rouse DJ. Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful. Am J Obstet Gynecol. 2014;211:124-127. 
  3. Althabe O, Schwarcz RL, Pose SV, et al. Effects on fetal heart rate and fetal pO2 of oxygen administration to the mother. Am J Obstet Gynecol. 1967;98:858-870. 
  4. Haydon ML, Gorenberg DM, Nageotte MP, et al. The effect of maternal oxygen administration on fetal pulse oximetry during labor in fetuses with nonreassuring fetal heart rate patterns. Am J Obstet Gynecol. 2006;195:735-738. 
  5. Fawole B, Hofmeyr GJ. Maternal oxygen administration for fetal distress. Cochrane Database Syst Rev. 2012;12:CD0000136. 
  6. McHugh A, El-Khuffash A, Bussmann N, et al. Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state. Am J Obstet Gynecol. 2019;220:397.e1-397.e8. 
  7. Khaw KS, Wang CC, Ngan Kee WD, et al. Effects of high inspired oxygen fraction during elective caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation. Br J Anaesth. 2002;88:18-23. 
  8. Watkins VY, Martin S, Macones GA, et al. The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content. Am J Obstet Gynecol. 2020;223:440.e1-440.e7. 
  9. Raghuraman N, Temming LA, Stout MJ, et al. Intrauterine hyperoxemia and risk of neonatal morbidity. Obstet Gynecol. 2017;129:676-682. 
  10. Thorp JA, Trobough T, Evans R, et al. The effect of maternal oxygen administration during the second stage of labor on umbilical cord blood gas values: a randomized controlled prospective trial. Am J Obstet Gynecol. 1995;172(2 pt 1):465-474. 
  11. Rabi Y, Rabi D, Yee W. Room air resuscitation of the depressed newborn: a systematic review and meta-analysis. Resuscitation. 2007;72:353-363. 
  12. COVID-19 FAQs for Obstetrician-Gynecologists, Obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed October 15, 2020.
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Dr. Harris is a Resident, Prisma Health Upstate Obstetrics and Gynecology Resident Program, Greenville, South Carolina. 

Dr. Ragonetti-Zebell is an academic generalist, Department of Obstetrics and Gynecology, Prisma Health Upstate, Greenville.  

The authors report no financial relationships relevant to this article. 
 

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Dr. Harris is a Resident, Prisma Health Upstate Obstetrics and Gynecology Resident Program, Greenville, South Carolina. 

Dr. Ragonetti-Zebell is an academic generalist, Department of Obstetrics and Gynecology, Prisma Health Upstate, Greenville.  

The authors report no financial relationships relevant to this article. 
 

Author and Disclosure Information

Dr. Harris is a Resident, Prisma Health Upstate Obstetrics and Gynecology Resident Program, Greenville, South Carolina. 

Dr. Ragonetti-Zebell is an academic generalist, Department of Obstetrics and Gynecology, Prisma Health Upstate, Greenville.  

The authors report no financial relationships relevant to this article. 
 

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CASE Heart rate tracing suggests fetal distress

Ms. M. presents for elective induction of labor at 39 weeks’ gestation. During the course of her labor, a Category II fetal heart rate (FHR) tracing is noted, and maternal oxygen is administered as part of the intrauterine resuscitative efforts. Her infant ultimately was delivered vaginally with an arterial cord blood pH of 7.1 and Apgar scores of 5 and 7.

Should intrauterine resuscitation include maternal oxygen administration?

It is a common sight on labor and delivery: An FHR monitoring strip is noted to be a Category II tracing. There may be fetal tachycardia, late decelerations, or perhaps decreased variability. The nurse or physician goes to the laboring mother’s room, checks cervical dilation, changes the patient’s position, and puts an oxygen mask over her face.

The American College of Obstetricians and Gynecologists (ACOG) lists maternal oxygen administration, most commonly at 10 L/min via a nonrebreather face mask, as an intrauterine resuscitative measure for Category II or Category III FHR tracings.1 Maternal oxygen is used to treat abnormal FHR tracings in approximately half of all births in the United States.2 Despite these recommendations and the frequency of its use, however, evidence is limited that maternal oxygenation improves neonatal outcome. In fact, there is emerging evidence of potential harm.

Why use oxygen?

The use of maternal oxygen supplementation intuitively makes sense. We know that certain abnormalities in FHR tracings can signal fetal hypoxia. Left untreated, the hypoxia could lead to fetal acidemia and associated neonatal sequelae. Theoretically, the administration of maternal oxygen should lead to improved fetal oxygenation and improved fetal outcome. This is supported by studies from the 1960s that demonstrate improved FHR tracings after maternal oxygen administration.3

This idea was further supported by studies that demonstrated an increase in fetal oxygen levels when maternal oxygen is administered. Haydon and colleagues evaluated the administration of maternal oxygen in women with nonreassuring FHR tracings.4 Their data showed that maternal oxygen administration increased fetal oxygen as measured by fetal pulse oximetry. The lower the initial fetal oxygen levels prior to oxygen administration, the greater the increase.

Despite these findings, evidence for improved neonatal outcomes is lacking.5 While heart rate tracings and fetal oxygen saturation may be improved with maternal oxygen supplementation, neonatal morbidity appears to remain unchanged (FIGURE). In fact, newer research suggests potential harm. Although an improved FHR tracing may be comforting to the clinician, the end result may be less so. Given these findings on maternal oxygen supplementation, it is time to break this practice habit.

Maternal cardiovascular effects

Most of the literature on maternal hyperoxygenation focuses on fetal response. Before examining the effects on the fetus, however, we must consider the effect on the mother. Cardiovascular changes occur during and after maternal oxygen administration that should be taken into account.

McHugh and colleagues measured the hemodynamic changes in 46 pregnant and 20 nonpregnant women before, immediately, and 10 minutes after a 30-minute period of high-flow oxygen administration.6 While there were no changes in the nonpregnant women’s parameters, in the pregnant women heart rate and stroke volume were decreased after oxygen administration. Additionally, systemic vascular resistance increased and did not return to baseline by 10 minutes postadministration.

Since the purpose of the maternal oxygen administration is to increase oxygen to the fetus, this decrease in cardiac output and increase in systemic vascular resistance is concerning. These results may negate the intended effect of increased oxygen delivery to the fetus.

Continue to: Maternal and fetal oxidative stress...

 

 

Maternal and fetal oxidative stress

Assuming that the abnormal FHR tracing in our case patient is actually due to fetal hypoxia, it would seem prudent to increase fetal oxygenation. However, fetal hyperoxygenation may lead to free radical damage that could worsen neonatal outcomes. Oxidative stress, which can be caused by both hypoxia and hyperoxia, can lead to endothelial and cell receptor damage. This is known to contribute to the cerebral damage of hypoxic-ischemic encephalopathy.

In a randomized trial, Khaw and colleagues measured lipid peroxidases as a “free radical footprint” in women undergoing elective cesarean delivery who were administered oxygen or room air.7 Maternal and fetal oxygen levels were higher in the oxygen-supplementation group, but lipid peroxidases also were elevated. This finding suggests that the excess oxygen results in free radical formation and potentially negative effects on the neonate.

Although maternal oxygen supplementation frequently is viewed as harmless, this research shows that free radical damage may occur in the mother as well.

Additional research shows that longer durations of oxygen administration are correlated with worsening neonatal outcomes. In a study of liberal versus indicated oxygen use, the average time was approximately 90 minutes.8 Use for longer than 176 minutes was associated with lower oxygen levels in fetal blood. A proposed mechanism for this response is placental vasoconstriction thought to protect the fetus from free radical damage.

Again, if the goal is to increase oxygenation, prolonged maternal oxygen supplementation appears to produce the opposite effect.

Fetal acidemia and neonatal morbidity

If a fetus with an abnormal FHR tracing is thought to be hypoxic or acidemic, adding the potentially harmful effects of free radicals could worsen this condition. This is exactly what Raghuraman and colleagues demonstrated in a large prospective cohort analysis.9 While there was no difference in neonatal morbidity between those receiving oxygen and those on room air, there was a significant difference among infants with acidemia and hyperoxia. Composite morbidity (mechanical ventilation, hypothermic therapy, meconium aspiration, and death) was significantly increased in neonates with both hyperoxia and acidemia compared with nonacidemic hyperoxic infants.9 This is further supported by reports of an increased need for neonatal resuscitation and a fourfold increase in umbilical cord pH of less than 7.2.10

While intrauterine and extrauterine life certainly differ, these findings align with the pediatric literature that supports neonatal resuscitation with room air rather than 100% oxygen.11 Additionally, the intrauterine environment is relatively hypoxic, which may make free radical damage more severe.

Continue to: Oxygen use during the COVID-19 pandemic...

 

 

Oxygen use during the COVID-19 pandemic

While high-flow oxygen by mask is not considered an aerosol-generating procedure according to the Centers for Disease Control and Prevention, data are limited regarding the cleaning and filtering of oxygen. It is unknown if high-flow oxygen by mask increases the risk of infectious disease transmission to care providers. Therefore, in the midst of the COVID-19 pandemic, ACOG currently recommends against using supplemental oxygen for Category II and Category III tracings, since the benefits are not well established and the possibility of harm to providers may be increased.12 Oxygen supplementation still should be used in mothers with hypoxia.

Other intrauterine resuscitation options

Maternal oxygen administration does not appear beneficial for neonatal outcomes, but other methods can be used. An intravenous fluid bolus and lateral positioning of the mother, for example, are both associated with increased fetal oxygenation. Reducing uterine activity by discontinuing oxytocin or cervical ripening agents or by administering a tocolytic also can improve FHR abnormalities. Oxygen use should be reserved for patients with maternal hypoxia.

The bottom line

The liberal use of maternal oxygenation for the management of abnormal FHR tracings should be stopped. Clear evidence of its benefit is lacking, and the real possibility of fetal and maternal harm remains. This may be especially true during the COVID-19 pandemic. ●

 

 

CASE Heart rate tracing suggests fetal distress

Ms. M. presents for elective induction of labor at 39 weeks’ gestation. During the course of her labor, a Category II fetal heart rate (FHR) tracing is noted, and maternal oxygen is administered as part of the intrauterine resuscitative efforts. Her infant ultimately was delivered vaginally with an arterial cord blood pH of 7.1 and Apgar scores of 5 and 7.

Should intrauterine resuscitation include maternal oxygen administration?

It is a common sight on labor and delivery: An FHR monitoring strip is noted to be a Category II tracing. There may be fetal tachycardia, late decelerations, or perhaps decreased variability. The nurse or physician goes to the laboring mother’s room, checks cervical dilation, changes the patient’s position, and puts an oxygen mask over her face.

The American College of Obstetricians and Gynecologists (ACOG) lists maternal oxygen administration, most commonly at 10 L/min via a nonrebreather face mask, as an intrauterine resuscitative measure for Category II or Category III FHR tracings.1 Maternal oxygen is used to treat abnormal FHR tracings in approximately half of all births in the United States.2 Despite these recommendations and the frequency of its use, however, evidence is limited that maternal oxygenation improves neonatal outcome. In fact, there is emerging evidence of potential harm.

Why use oxygen?

The use of maternal oxygen supplementation intuitively makes sense. We know that certain abnormalities in FHR tracings can signal fetal hypoxia. Left untreated, the hypoxia could lead to fetal acidemia and associated neonatal sequelae. Theoretically, the administration of maternal oxygen should lead to improved fetal oxygenation and improved fetal outcome. This is supported by studies from the 1960s that demonstrate improved FHR tracings after maternal oxygen administration.3

This idea was further supported by studies that demonstrated an increase in fetal oxygen levels when maternal oxygen is administered. Haydon and colleagues evaluated the administration of maternal oxygen in women with nonreassuring FHR tracings.4 Their data showed that maternal oxygen administration increased fetal oxygen as measured by fetal pulse oximetry. The lower the initial fetal oxygen levels prior to oxygen administration, the greater the increase.

Despite these findings, evidence for improved neonatal outcomes is lacking.5 While heart rate tracings and fetal oxygen saturation may be improved with maternal oxygen supplementation, neonatal morbidity appears to remain unchanged (FIGURE). In fact, newer research suggests potential harm. Although an improved FHR tracing may be comforting to the clinician, the end result may be less so. Given these findings on maternal oxygen supplementation, it is time to break this practice habit.

Maternal cardiovascular effects

Most of the literature on maternal hyperoxygenation focuses on fetal response. Before examining the effects on the fetus, however, we must consider the effect on the mother. Cardiovascular changes occur during and after maternal oxygen administration that should be taken into account.

McHugh and colleagues measured the hemodynamic changes in 46 pregnant and 20 nonpregnant women before, immediately, and 10 minutes after a 30-minute period of high-flow oxygen administration.6 While there were no changes in the nonpregnant women’s parameters, in the pregnant women heart rate and stroke volume were decreased after oxygen administration. Additionally, systemic vascular resistance increased and did not return to baseline by 10 minutes postadministration.

Since the purpose of the maternal oxygen administration is to increase oxygen to the fetus, this decrease in cardiac output and increase in systemic vascular resistance is concerning. These results may negate the intended effect of increased oxygen delivery to the fetus.

Continue to: Maternal and fetal oxidative stress...

 

 

Maternal and fetal oxidative stress

Assuming that the abnormal FHR tracing in our case patient is actually due to fetal hypoxia, it would seem prudent to increase fetal oxygenation. However, fetal hyperoxygenation may lead to free radical damage that could worsen neonatal outcomes. Oxidative stress, which can be caused by both hypoxia and hyperoxia, can lead to endothelial and cell receptor damage. This is known to contribute to the cerebral damage of hypoxic-ischemic encephalopathy.

In a randomized trial, Khaw and colleagues measured lipid peroxidases as a “free radical footprint” in women undergoing elective cesarean delivery who were administered oxygen or room air.7 Maternal and fetal oxygen levels were higher in the oxygen-supplementation group, but lipid peroxidases also were elevated. This finding suggests that the excess oxygen results in free radical formation and potentially negative effects on the neonate.

Although maternal oxygen supplementation frequently is viewed as harmless, this research shows that free radical damage may occur in the mother as well.

Additional research shows that longer durations of oxygen administration are correlated with worsening neonatal outcomes. In a study of liberal versus indicated oxygen use, the average time was approximately 90 minutes.8 Use for longer than 176 minutes was associated with lower oxygen levels in fetal blood. A proposed mechanism for this response is placental vasoconstriction thought to protect the fetus from free radical damage.

Again, if the goal is to increase oxygenation, prolonged maternal oxygen supplementation appears to produce the opposite effect.

Fetal acidemia and neonatal morbidity

If a fetus with an abnormal FHR tracing is thought to be hypoxic or acidemic, adding the potentially harmful effects of free radicals could worsen this condition. This is exactly what Raghuraman and colleagues demonstrated in a large prospective cohort analysis.9 While there was no difference in neonatal morbidity between those receiving oxygen and those on room air, there was a significant difference among infants with acidemia and hyperoxia. Composite morbidity (mechanical ventilation, hypothermic therapy, meconium aspiration, and death) was significantly increased in neonates with both hyperoxia and acidemia compared with nonacidemic hyperoxic infants.9 This is further supported by reports of an increased need for neonatal resuscitation and a fourfold increase in umbilical cord pH of less than 7.2.10

While intrauterine and extrauterine life certainly differ, these findings align with the pediatric literature that supports neonatal resuscitation with room air rather than 100% oxygen.11 Additionally, the intrauterine environment is relatively hypoxic, which may make free radical damage more severe.

Continue to: Oxygen use during the COVID-19 pandemic...

 

 

Oxygen use during the COVID-19 pandemic

While high-flow oxygen by mask is not considered an aerosol-generating procedure according to the Centers for Disease Control and Prevention, data are limited regarding the cleaning and filtering of oxygen. It is unknown if high-flow oxygen by mask increases the risk of infectious disease transmission to care providers. Therefore, in the midst of the COVID-19 pandemic, ACOG currently recommends against using supplemental oxygen for Category II and Category III tracings, since the benefits are not well established and the possibility of harm to providers may be increased.12 Oxygen supplementation still should be used in mothers with hypoxia.

Other intrauterine resuscitation options

Maternal oxygen administration does not appear beneficial for neonatal outcomes, but other methods can be used. An intravenous fluid bolus and lateral positioning of the mother, for example, are both associated with increased fetal oxygenation. Reducing uterine activity by discontinuing oxytocin or cervical ripening agents or by administering a tocolytic also can improve FHR abnormalities. Oxygen use should be reserved for patients with maternal hypoxia.

The bottom line

The liberal use of maternal oxygenation for the management of abnormal FHR tracings should be stopped. Clear evidence of its benefit is lacking, and the real possibility of fetal and maternal harm remains. This may be especially true during the COVID-19 pandemic. ●

References
  1. American College of Obstetricians and Gynecologists. Practice bulletin No. 116. Management of intrapartum fetal heart rate tracings. Obstet Gynecol. 2010;116:1232-1240. 
  2. Hamel MS, Anderson BL, Rouse DJ. Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful. Am J Obstet Gynecol. 2014;211:124-127. 
  3. Althabe O, Schwarcz RL, Pose SV, et al. Effects on fetal heart rate and fetal pO2 of oxygen administration to the mother. Am J Obstet Gynecol. 1967;98:858-870. 
  4. Haydon ML, Gorenberg DM, Nageotte MP, et al. The effect of maternal oxygen administration on fetal pulse oximetry during labor in fetuses with nonreassuring fetal heart rate patterns. Am J Obstet Gynecol. 2006;195:735-738. 
  5. Fawole B, Hofmeyr GJ. Maternal oxygen administration for fetal distress. Cochrane Database Syst Rev. 2012;12:CD0000136. 
  6. McHugh A, El-Khuffash A, Bussmann N, et al. Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state. Am J Obstet Gynecol. 2019;220:397.e1-397.e8. 
  7. Khaw KS, Wang CC, Ngan Kee WD, et al. Effects of high inspired oxygen fraction during elective caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation. Br J Anaesth. 2002;88:18-23. 
  8. Watkins VY, Martin S, Macones GA, et al. The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content. Am J Obstet Gynecol. 2020;223:440.e1-440.e7. 
  9. Raghuraman N, Temming LA, Stout MJ, et al. Intrauterine hyperoxemia and risk of neonatal morbidity. Obstet Gynecol. 2017;129:676-682. 
  10. Thorp JA, Trobough T, Evans R, et al. The effect of maternal oxygen administration during the second stage of labor on umbilical cord blood gas values: a randomized controlled prospective trial. Am J Obstet Gynecol. 1995;172(2 pt 1):465-474. 
  11. Rabi Y, Rabi D, Yee W. Room air resuscitation of the depressed newborn: a systematic review and meta-analysis. Resuscitation. 2007;72:353-363. 
  12. COVID-19 FAQs for Obstetrician-Gynecologists, Obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed October 15, 2020.
References
  1. American College of Obstetricians and Gynecologists. Practice bulletin No. 116. Management of intrapartum fetal heart rate tracings. Obstet Gynecol. 2010;116:1232-1240. 
  2. Hamel MS, Anderson BL, Rouse DJ. Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful. Am J Obstet Gynecol. 2014;211:124-127. 
  3. Althabe O, Schwarcz RL, Pose SV, et al. Effects on fetal heart rate and fetal pO2 of oxygen administration to the mother. Am J Obstet Gynecol. 1967;98:858-870. 
  4. Haydon ML, Gorenberg DM, Nageotte MP, et al. The effect of maternal oxygen administration on fetal pulse oximetry during labor in fetuses with nonreassuring fetal heart rate patterns. Am J Obstet Gynecol. 2006;195:735-738. 
  5. Fawole B, Hofmeyr GJ. Maternal oxygen administration for fetal distress. Cochrane Database Syst Rev. 2012;12:CD0000136. 
  6. McHugh A, El-Khuffash A, Bussmann N, et al. Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state. Am J Obstet Gynecol. 2019;220:397.e1-397.e8. 
  7. Khaw KS, Wang CC, Ngan Kee WD, et al. Effects of high inspired oxygen fraction during elective caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation. Br J Anaesth. 2002;88:18-23. 
  8. Watkins VY, Martin S, Macones GA, et al. The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content. Am J Obstet Gynecol. 2020;223:440.e1-440.e7. 
  9. Raghuraman N, Temming LA, Stout MJ, et al. Intrauterine hyperoxemia and risk of neonatal morbidity. Obstet Gynecol. 2017;129:676-682. 
  10. Thorp JA, Trobough T, Evans R, et al. The effect of maternal oxygen administration during the second stage of labor on umbilical cord blood gas values: a randomized controlled prospective trial. Am J Obstet Gynecol. 1995;172(2 pt 1):465-474. 
  11. Rabi Y, Rabi D, Yee W. Room air resuscitation of the depressed newborn: a systematic review and meta-analysis. Resuscitation. 2007;72:353-363. 
  12. COVID-19 FAQs for Obstetrician-Gynecologists, Obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed October 15, 2020.
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Surprisingly, in the United States, the most common cancer associated with human papillomavirus (HPV) is oropharyngeal squamous cell cancer (SCC), with one study reporting 15,479 cases among men and 3,428 cases among women in 2015.1 In the same year, the investigators reported 11,788 cases of cervical cancer.1 A public health concern is that cases of oropharyngeal SCC are increasing, while cases of cervical cancer are decreasing. From 1999 to 2015, the rate of oropharyngeal SCC increased annually among both men and women, at rates of 2.7% and 0.8% per year, respectively. By contrast, the rate of cervical cancer decreased by 1.6% per year.1

Although the incidence of HPV-negative oropharyngeal SCC (cases associated with cigarette smoking) has declined by 50% from 1988 to 2004, the incidence of HPV-positive oropharyngeal SCC has increased by 225%, with much of the increase occurring among young, white men.2 HPV infection is a major cause of oropharyngeal SCC at the base of the tongue and tonsils, but not in the soft palate or oropharyngeal walls.3

Most physicians and parents recognize that the 9-valent (9v)HPV vaccine prevents the majority of cervical cancers and precancers in women. Far fewer people realize that there is an important opportunity to prevent a large number of oropharyngeal cancers by improving 9vHPV vaccination in men and women.

Which HPV types are associated with oropharyngeal cancer?

HPV16 is the most common HPV type associated with oropharyngeal SCC. Among these cancer types, greater than 80% harbor HPV16, with greater than 90% harboring HPV16 or 18 and less than 10% of tumors associated with HPV types 31, 33, 45, 52, or 58.4-7

The high prevalence of HPV16 in patients with oropharyngeal cancer raises the question of the HPV status of the intimate partner of the index patient. In one study of 164 people with HPV detected in their oropharyngeal, the partner of the index patient had a low prevalence of high-risk HPV types (1.2%) in oral rinse and gargle samples, similar to the rate in the general population (1.3%).7 This finding is reassuring and suggests that intimate partners of patients with HPV-positive oropharyngeal cancer effectively clear high-risk HPV virus from the oropharynx. The HPV status of the genital tissue of the intimate partner of an index patient with oropharyngeal SCC has not been adequately studied.

Men are more likely than women to harbor oral HPV

Among a sample of 5,501 men and women aged 14 to 69 years from the National Health and Nutrition Examination Survey, oral rinses were obtained and analyzed for the presence of HPV.8 The prevalence of any oral HPV and any oral high-risk HPV was 6.9% and 3.7%, respectively. Oral HPV-16 was detected in 1.6% of men and 0.3% of women. The prevalence of HPV was higher among current smokers, heavy alcohol drinkers, and people with a history of a greater number of sexual partners. In men and women reporting more than 20 lifetime sexual partners, the prevalence of oral HPV was 20%.

In a study of 2,627 men and women aged 18 to 33 years, the prevalence of oral HPV 16/18/6/11 was lower among those vaccinated versus those unvaccinated (0.11% and 1.6%, respectively; P = .008).9 Among men, oral HPV 16/18/6/11 was lower among those vaccinated versus unvaccinated (0.0% and 2.13%, respectively; P = .007).9 The results of this observational study support the important role of vaccination in reducing oral HPV infection.

9vHPV vaccine: Indications and immunization schedule

In 2020, the US Food and Drug Administration (FDA) approved the 9-valent human papillomavirus (9vHPV) vaccine for the prevention of oropharyngeal cancer. The 9vHPV vaccine contains inactive L1 capsid proteins for 9 HPV types, including types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The vaccine stimulates the production of neutralizing antibodies to the capsid protein.

9vHPV is approved for females aged 9 to 45 years to prevent cancers and precancers of the cervix, vulva, vagina, and anus caused by HPV types 16, 18, 31, 33, 45, 52, and 58.1 It is also approved for males aged 9 to 45 years to prevent cancer and precancers of the anus caused by those viral types. In 2020 the 9vHPV vaccine was approved by the FDA to prevent oropharyngeal cancer in males and females. Of note, the FDA reported that, “the oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”2

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of girls and boys, 11 to 12 years of age.1 Children with a history of sexual abuse or assault can start the vaccine at 9 years of age. Catch-up vaccination is recommended for all females and males through age 26 years. The ACIP recommends shared clinical decision-making regarding vaccination for some adults 27 to 45 years of age. Gynecologists with routine exposure to HPV may have occupational risk that warrants HPV vaccination3 (see “As a gynecologist, should you receive the 9vHPV vaccine?”).

For most individuals who start the vaccine series before age 15, two doses of 9vHPV vaccine are recommended, with the second dose 6 to 12 months following the first dose. For teens and adults aged 15 to 26 years, 3 doses of 9vHPV vaccine are recommended, with the second dose 1 to 2 months later and the third dose 6 months following the first dose. Immunocompromised individuals 9 to 26 years of age, including those with HIV infection, should receive 3 doses of the vaccine.

References

1. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.

2. Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck & Co. Inc; 2020.

3. Stockdale CK, Einstein MH, Huh WK. ASCCP recommends HPV vaccination for providers. February 19, 2020. https://www.asccp.org/Assets/d3abdb05-25c5-4e58-9cec-05c11fb2b920/637177876310030000/hpv-vaccinemember-announcment-02-19-20-pdf. Accessed October 23, 2020.

Continue to: Vaccinate boys and girls to prevent cancer...

 

 

Vaccinate boys and girls to prevent cancer

Most population studies report that males are less likely to receive an HPV vaccine than females. For example, based on the National Health Interview Survey of people aged 18 to 26, the percentage of women who self-reported receiving at least one dose of HPV vaccine was 37% in 2013 and 54% in 2018.10 By contrast, among men, the rates of self-reported vaccination were much lower—8% in 2013 and 27% in 2018.10

The percentage of women who received the recommended number of doses of HPV vaccine (see “9vHPV vaccine: Indications and immunization schedule”) was 26% in 2013 and 35% in 2018.10 For men, these percentages were 2% in 2013 and 9% in 2018.10 These data indicate that, compared with women, men are less likely to receive an HPV vaccination and far less likely to have received the recommended number of doses.

It is heartening that there has been a slow and steady increase in the prevalence of HPV vaccination. In fact, increasing the HPV vaccination rate among both boys and girls has the potential to markedly reduce the incidence of oropharyngeal cancer.

The reasons for the female-male gap in vaccination rates are not fully characterized. For one, parental awareness of the importance of HPV vaccination to prevent cancer among men is limited, and represents an important opportunity for additional public health education. In a qualitative interview study of mothers with children aged 11 to 19, the investigators reported that most mothers were aware that HPV vaccination could prevent cervical cancer in women, but most mothers did not know that HPV causes cancer of the mouth and that vaccination could prevent oropharyngeal cancer in boys and girls.11 Because of this lack of knowledge, the mothers did not think their sons needed to have an HPV vaccine. The research report is aptly titled, “I don’t think he needs the HPV vaccine cause boys can’t have cervical cancer.”11

Clinicians are highly influential in guiding parents to accept HPV vaccination of their children. Offering consistent messaging to parents that HPV vaccination prevents cancer in both women and men, and reducing the out-of-pocket cost of vaccination surely will result in an increase in the vaccination rate of boys and girls. ●

As a gynecologist, should you receive the 9vHPV vaccine?

Surgical treatment of tissues infected with human papillomavirus (HPV) often involves the use of laser or electrosurgical devices that generate smoke, which is known to contain HPV nucleic acid sequences and may contain infective virions.1 It is known that HPV nucleic acid sequences are present in surgical smoke. In one study plantar warts were treated with a carbon dioxide laser or electrocoagulation. The vapor produced from the surgery was collected with a dry filter apparatus. Five of 8 laser-derived vapors and 4 of 7 electrocoagulation-derived vapors were positive for HPV DNA. The concentration of HPV DNA was greater with laser than with electrocoagulation treatment.2

It is not known if surgical smoke derived from treatment of HPV-infected tissues contains infective HPV virions. In an experimental bovine model, smoke generated by laser ablation of fibropapillomas was collected. Injection of the contents of the smoke caused cutaneous papillomavirus lesions when inoculated into calves, suggesting that the smoke contained infective HPV virions.3 Although this animal experiment is a proof of principle that surgical smoke generated from treatment of HPVinfected tissue contain virions, it is unclear if surgical smoke generated in gynecologic practice contains HPV virions.

To investigate the prevalence of nasal HPV DNA among gynecologists, 700 physicians in Zhejiang Province, China, completed a questionnaire and provided a nasal swab for HPV DNA analysis.4 Among gynecologists who performed or did not perform LEEP, the prevalence of HPV DNA in the nose was 10% and 3%, respectively. The most common HPV types detected were HPV16 (76%), HPV31 (10%), HPV58 (5%), HPV55 (5%), HPV56 (2%), and HPV59 (2%).4 Among gynecologists who performed LEEP procedures, the prevalence of HPV DNA was 19% for those who did not use a surgical mask, 8% for clinicians who used a standard surgical mask, and 0% for those who used an N95 filtering facepiece respirator, suggesting that an N95 respirator provides the greatest protection from surgical smoke.4 Over 24 months of follow-up, all the gynecologists who had initially tested positive for HPV DNA no longer had detectable nasal HPV DNA. In this study, no gynecologist was diagnosed with an HPV-associated oropharyngeal disease. The investigators concluded that surgical masks, especially an N95 respirator, should be used by gynecologists performing LEEP procedures.

Investigators also have evaluated for the presence of HPV DNA in matched samples from the cervix of 134 patients undergoing loop electrosurgical excision procedure (LEEP) for cervical dysplasia, as well as the smoke generated during the procedure and nasal swabs from the surgeon performing the LEEP.5 HPV DNA was detected in 95% of the cervical samples, 30% of the surgical smoke samples, and 1.5% of the surgeons’ nasal swabs.5 At 6 months of follow-up, the two surgeons who initially had HPV-positive nasal swabs no longer had detected HPV DNA.

Of concern is that otolaryngologists have reported sporadic cases of oropharyngeal squamous cell cancer6 and laryngeal papillomatosis7 in health care workers with frequent and repetitive exposure to HPVs. For example, in one case report, a 53-year-old male gynecologist, nonsmoker, presented to his physician with a lump on the neck.6 The gynecologist had performed more than 3,000 laser ablation or LEEP procedures of dysplastic cervical, vaginal, and vulvar lesions over a span of 20 years.6 Most of the procedures were performed without wearing a mask and in a poorly ventilated procedure room. A computed tomography scan demonstrated a 2.2-cm soft tissue lesion in the right tonsil extending to the right soft palate and a level-2 lymph node. A biopsy of the tonsil confirmed invasive squamous cell carcinoma containing HPV16. He was treated with 35 fractions of radiotherapy and adjuvant cisplatin. Treatment adverse effects included dysphagia and xerostomia, and the patient lost 40 pounds.

Available interventions to reduce exposure of clinicians to HPV virions that may be present in surgical smoke include:

  • wearing a fit-tested N95 respirator  
  • routinely using a smoke evacuation device, and
  • ensuring sufficient ventilation in the procedure room.

A new recommendation is to consider 9vHPV vaccination for clinicians who are routinely exposed to HPV virions.8,9 In February 2020, the American Society for Colposcopy and Cervical Pathology recommended that clinicians who are routinely exposed to HPVs consider 9vHPV vaccination.8 This recommendation pertains to all members of the clinical team in the procedure room, including physicians, nurses, and staff. Based on the available data, gynecologists who have not been vaccinated will need to weigh the benefits and costs of receiving a 9vHPV vaccine to protect themselves against an occupational exposure that may adversely impact their health.

References

  1. Liu Y, Song Y, Hu X, et al. Awareness of surgical smoke hazards and enhancement of surgical smoke prevention among gynecologists. J Cancer. 2019;10:2788-2799.
  2. Sawchuk WS, Weber PJ, Lowy DR, et al. Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: detection and protection. J Am Acad Dermatol. 1989;21:41-49.
  3. Garden JM, O’Banion MK, Bakus AD, et al. Viral transmitted by laser-generated plume (aerosol). Arch Dermatol. 2002;138:1303-1307.
  4. Hu X, Zhou Q, Yu J, et al. Prevalence of HPV infections in surgical smoke exposed gynecologists. Int Arch Occup Environ Health. 2020; Epub September 1. doi: 10.1007 /s00420-020-01568-9.
  5. Zhou Q, Hu X, Zhou J, et al. Human papillomavirus DNA in surgical smoke during cervical loop electrosurgical excision procedures and its impact on the surgeon. Cancer Manag Res. 2019;11:3643-3654.
  6. Rioux M, Garland A, Webster D, et al. HPV-positive tonsillar cancer in two laser surgeons: case reports. J Otolaryngol Head Neck Surg. 2013;42:54-57.
  7. Hallmo P, Naess O. Laryngeal papillomatosis with human papillomavirus DNA contracted by a laser surgeon. Eur Arch Otorhinolaryngol. 1991;248:425-427.
  8. Stockdale CK, Einstein MH, Huh WK. ASCCP recommends HPV vaccination for providers. February 19, 2020. www.asccp.org/Assets/d3abdb05-25c5-4e58-%209cec-05c11fb2b920/637177876310030000/hpv-vaccinemember-announcment-02-19-20-pdf. Accessed October 23, 2020.

  9. Harrison R, Huh W. Occupational exposure to human papillomavirus and vaccination for health care workers. Obstet Gynecol. 2020;136:663-665

 

 

References
  1. Van Dyne EA, Henley SJ, Saraiya M, et al. Trends in human papillomavirus-associated cancers--United States, 1999-2015. MMWR. 2018;67:918-924. 
  2. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294-4301. 
  3. Haeggblom L, Ramqvist T, Tommasino M, et al. Time to change perspective on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years. Papillomavirus Research. 2017;4:1-11. 
  4. Kreimer AR, Clifford GM, Boyle P, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467-475.  
  5. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944-1956. 
  6. de Martel C, Plummer M, Vignat J, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141:664-670. 
  7. D'Souza G, Gross ND, Pai SI, et al. Oral human papillomavirus infection in HPV-positive patients with oropharyngeal cancer and their partners. J Clin Oncol. 2014;32:2408-2415. 
  8. Gillison ML, Broutian T, Pickard RK, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307:693. 
  9. Chaturvedi AK, Graubard BI, Broutian T, et al. Effect of prophylactic human papillomavirus vaccination on oral HPV infections among young adults in the United States. J Clin Oncol. 2018;36:262-267. 
  10. Boersma P, Black LI. Human papillomavirus vaccination among adults aged 18 to 26, 2013-2018. NCHS Data Brief. 2020:1-8. 
  11. Lindsay AC, Delgado D, Valdez MJ, et al. "I don't think he needs the HPV vaccine cause boys can't have cervical cancer": a qualitative study of Latina mothers' (Mis) understandings about human papillomavirus transmission, associated cancers and the vaccine. J Cancer Educ. July 11, 2020. doi: 10.1007/s13187-020-01824-z.
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Harvard Medical School
Boston, Massachusetts

Dr. Barbieri reports no financial relationships relevant to this article.

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Harvard Medical School
Boston, Massachusetts

Dr. Barbieri reports no financial relationships relevant to this article.

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Surprisingly, in the United States, the most common cancer associated with human papillomavirus (HPV) is oropharyngeal squamous cell cancer (SCC), with one study reporting 15,479 cases among men and 3,428 cases among women in 2015.1 In the same year, the investigators reported 11,788 cases of cervical cancer.1 A public health concern is that cases of oropharyngeal SCC are increasing, while cases of cervical cancer are decreasing. From 1999 to 2015, the rate of oropharyngeal SCC increased annually among both men and women, at rates of 2.7% and 0.8% per year, respectively. By contrast, the rate of cervical cancer decreased by 1.6% per year.1

Although the incidence of HPV-negative oropharyngeal SCC (cases associated with cigarette smoking) has declined by 50% from 1988 to 2004, the incidence of HPV-positive oropharyngeal SCC has increased by 225%, with much of the increase occurring among young, white men.2 HPV infection is a major cause of oropharyngeal SCC at the base of the tongue and tonsils, but not in the soft palate or oropharyngeal walls.3

Most physicians and parents recognize that the 9-valent (9v)HPV vaccine prevents the majority of cervical cancers and precancers in women. Far fewer people realize that there is an important opportunity to prevent a large number of oropharyngeal cancers by improving 9vHPV vaccination in men and women.

Which HPV types are associated with oropharyngeal cancer?

HPV16 is the most common HPV type associated with oropharyngeal SCC. Among these cancer types, greater than 80% harbor HPV16, with greater than 90% harboring HPV16 or 18 and less than 10% of tumors associated with HPV types 31, 33, 45, 52, or 58.4-7

The high prevalence of HPV16 in patients with oropharyngeal cancer raises the question of the HPV status of the intimate partner of the index patient. In one study of 164 people with HPV detected in their oropharyngeal, the partner of the index patient had a low prevalence of high-risk HPV types (1.2%) in oral rinse and gargle samples, similar to the rate in the general population (1.3%).7 This finding is reassuring and suggests that intimate partners of patients with HPV-positive oropharyngeal cancer effectively clear high-risk HPV virus from the oropharynx. The HPV status of the genital tissue of the intimate partner of an index patient with oropharyngeal SCC has not been adequately studied.

Men are more likely than women to harbor oral HPV

Among a sample of 5,501 men and women aged 14 to 69 years from the National Health and Nutrition Examination Survey, oral rinses were obtained and analyzed for the presence of HPV.8 The prevalence of any oral HPV and any oral high-risk HPV was 6.9% and 3.7%, respectively. Oral HPV-16 was detected in 1.6% of men and 0.3% of women. The prevalence of HPV was higher among current smokers, heavy alcohol drinkers, and people with a history of a greater number of sexual partners. In men and women reporting more than 20 lifetime sexual partners, the prevalence of oral HPV was 20%.

In a study of 2,627 men and women aged 18 to 33 years, the prevalence of oral HPV 16/18/6/11 was lower among those vaccinated versus those unvaccinated (0.11% and 1.6%, respectively; P = .008).9 Among men, oral HPV 16/18/6/11 was lower among those vaccinated versus unvaccinated (0.0% and 2.13%, respectively; P = .007).9 The results of this observational study support the important role of vaccination in reducing oral HPV infection.

9vHPV vaccine: Indications and immunization schedule

In 2020, the US Food and Drug Administration (FDA) approved the 9-valent human papillomavirus (9vHPV) vaccine for the prevention of oropharyngeal cancer. The 9vHPV vaccine contains inactive L1 capsid proteins for 9 HPV types, including types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The vaccine stimulates the production of neutralizing antibodies to the capsid protein.

9vHPV is approved for females aged 9 to 45 years to prevent cancers and precancers of the cervix, vulva, vagina, and anus caused by HPV types 16, 18, 31, 33, 45, 52, and 58.1 It is also approved for males aged 9 to 45 years to prevent cancer and precancers of the anus caused by those viral types. In 2020 the 9vHPV vaccine was approved by the FDA to prevent oropharyngeal cancer in males and females. Of note, the FDA reported that, “the oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”2

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of girls and boys, 11 to 12 years of age.1 Children with a history of sexual abuse or assault can start the vaccine at 9 years of age. Catch-up vaccination is recommended for all females and males through age 26 years. The ACIP recommends shared clinical decision-making regarding vaccination for some adults 27 to 45 years of age. Gynecologists with routine exposure to HPV may have occupational risk that warrants HPV vaccination3 (see “As a gynecologist, should you receive the 9vHPV vaccine?”).

For most individuals who start the vaccine series before age 15, two doses of 9vHPV vaccine are recommended, with the second dose 6 to 12 months following the first dose. For teens and adults aged 15 to 26 years, 3 doses of 9vHPV vaccine are recommended, with the second dose 1 to 2 months later and the third dose 6 months following the first dose. Immunocompromised individuals 9 to 26 years of age, including those with HIV infection, should receive 3 doses of the vaccine.

References

1. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.

2. Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck & Co. Inc; 2020.

3. Stockdale CK, Einstein MH, Huh WK. ASCCP recommends HPV vaccination for providers. February 19, 2020. https://www.asccp.org/Assets/d3abdb05-25c5-4e58-9cec-05c11fb2b920/637177876310030000/hpv-vaccinemember-announcment-02-19-20-pdf. Accessed October 23, 2020.

Continue to: Vaccinate boys and girls to prevent cancer...

 

 

Vaccinate boys and girls to prevent cancer

Most population studies report that males are less likely to receive an HPV vaccine than females. For example, based on the National Health Interview Survey of people aged 18 to 26, the percentage of women who self-reported receiving at least one dose of HPV vaccine was 37% in 2013 and 54% in 2018.10 By contrast, among men, the rates of self-reported vaccination were much lower—8% in 2013 and 27% in 2018.10

The percentage of women who received the recommended number of doses of HPV vaccine (see “9vHPV vaccine: Indications and immunization schedule”) was 26% in 2013 and 35% in 2018.10 For men, these percentages were 2% in 2013 and 9% in 2018.10 These data indicate that, compared with women, men are less likely to receive an HPV vaccination and far less likely to have received the recommended number of doses.

It is heartening that there has been a slow and steady increase in the prevalence of HPV vaccination. In fact, increasing the HPV vaccination rate among both boys and girls has the potential to markedly reduce the incidence of oropharyngeal cancer.

The reasons for the female-male gap in vaccination rates are not fully characterized. For one, parental awareness of the importance of HPV vaccination to prevent cancer among men is limited, and represents an important opportunity for additional public health education. In a qualitative interview study of mothers with children aged 11 to 19, the investigators reported that most mothers were aware that HPV vaccination could prevent cervical cancer in women, but most mothers did not know that HPV causes cancer of the mouth and that vaccination could prevent oropharyngeal cancer in boys and girls.11 Because of this lack of knowledge, the mothers did not think their sons needed to have an HPV vaccine. The research report is aptly titled, “I don’t think he needs the HPV vaccine cause boys can’t have cervical cancer.”11

Clinicians are highly influential in guiding parents to accept HPV vaccination of their children. Offering consistent messaging to parents that HPV vaccination prevents cancer in both women and men, and reducing the out-of-pocket cost of vaccination surely will result in an increase in the vaccination rate of boys and girls. ●

As a gynecologist, should you receive the 9vHPV vaccine?

Surgical treatment of tissues infected with human papillomavirus (HPV) often involves the use of laser or electrosurgical devices that generate smoke, which is known to contain HPV nucleic acid sequences and may contain infective virions.1 It is known that HPV nucleic acid sequences are present in surgical smoke. In one study plantar warts were treated with a carbon dioxide laser or electrocoagulation. The vapor produced from the surgery was collected with a dry filter apparatus. Five of 8 laser-derived vapors and 4 of 7 electrocoagulation-derived vapors were positive for HPV DNA. The concentration of HPV DNA was greater with laser than with electrocoagulation treatment.2

It is not known if surgical smoke derived from treatment of HPV-infected tissues contains infective HPV virions. In an experimental bovine model, smoke generated by laser ablation of fibropapillomas was collected. Injection of the contents of the smoke caused cutaneous papillomavirus lesions when inoculated into calves, suggesting that the smoke contained infective HPV virions.3 Although this animal experiment is a proof of principle that surgical smoke generated from treatment of HPVinfected tissue contain virions, it is unclear if surgical smoke generated in gynecologic practice contains HPV virions.

To investigate the prevalence of nasal HPV DNA among gynecologists, 700 physicians in Zhejiang Province, China, completed a questionnaire and provided a nasal swab for HPV DNA analysis.4 Among gynecologists who performed or did not perform LEEP, the prevalence of HPV DNA in the nose was 10% and 3%, respectively. The most common HPV types detected were HPV16 (76%), HPV31 (10%), HPV58 (5%), HPV55 (5%), HPV56 (2%), and HPV59 (2%).4 Among gynecologists who performed LEEP procedures, the prevalence of HPV DNA was 19% for those who did not use a surgical mask, 8% for clinicians who used a standard surgical mask, and 0% for those who used an N95 filtering facepiece respirator, suggesting that an N95 respirator provides the greatest protection from surgical smoke.4 Over 24 months of follow-up, all the gynecologists who had initially tested positive for HPV DNA no longer had detectable nasal HPV DNA. In this study, no gynecologist was diagnosed with an HPV-associated oropharyngeal disease. The investigators concluded that surgical masks, especially an N95 respirator, should be used by gynecologists performing LEEP procedures.

Investigators also have evaluated for the presence of HPV DNA in matched samples from the cervix of 134 patients undergoing loop electrosurgical excision procedure (LEEP) for cervical dysplasia, as well as the smoke generated during the procedure and nasal swabs from the surgeon performing the LEEP.5 HPV DNA was detected in 95% of the cervical samples, 30% of the surgical smoke samples, and 1.5% of the surgeons’ nasal swabs.5 At 6 months of follow-up, the two surgeons who initially had HPV-positive nasal swabs no longer had detected HPV DNA.

Of concern is that otolaryngologists have reported sporadic cases of oropharyngeal squamous cell cancer6 and laryngeal papillomatosis7 in health care workers with frequent and repetitive exposure to HPVs. For example, in one case report, a 53-year-old male gynecologist, nonsmoker, presented to his physician with a lump on the neck.6 The gynecologist had performed more than 3,000 laser ablation or LEEP procedures of dysplastic cervical, vaginal, and vulvar lesions over a span of 20 years.6 Most of the procedures were performed without wearing a mask and in a poorly ventilated procedure room. A computed tomography scan demonstrated a 2.2-cm soft tissue lesion in the right tonsil extending to the right soft palate and a level-2 lymph node. A biopsy of the tonsil confirmed invasive squamous cell carcinoma containing HPV16. He was treated with 35 fractions of radiotherapy and adjuvant cisplatin. Treatment adverse effects included dysphagia and xerostomia, and the patient lost 40 pounds.

Available interventions to reduce exposure of clinicians to HPV virions that may be present in surgical smoke include:

  • wearing a fit-tested N95 respirator  
  • routinely using a smoke evacuation device, and
  • ensuring sufficient ventilation in the procedure room.

A new recommendation is to consider 9vHPV vaccination for clinicians who are routinely exposed to HPV virions.8,9 In February 2020, the American Society for Colposcopy and Cervical Pathology recommended that clinicians who are routinely exposed to HPVs consider 9vHPV vaccination.8 This recommendation pertains to all members of the clinical team in the procedure room, including physicians, nurses, and staff. Based on the available data, gynecologists who have not been vaccinated will need to weigh the benefits and costs of receiving a 9vHPV vaccine to protect themselves against an occupational exposure that may adversely impact their health.

References

  1. Liu Y, Song Y, Hu X, et al. Awareness of surgical smoke hazards and enhancement of surgical smoke prevention among gynecologists. J Cancer. 2019;10:2788-2799.
  2. Sawchuk WS, Weber PJ, Lowy DR, et al. Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: detection and protection. J Am Acad Dermatol. 1989;21:41-49.
  3. Garden JM, O’Banion MK, Bakus AD, et al. Viral transmitted by laser-generated plume (aerosol). Arch Dermatol. 2002;138:1303-1307.
  4. Hu X, Zhou Q, Yu J, et al. Prevalence of HPV infections in surgical smoke exposed gynecologists. Int Arch Occup Environ Health. 2020; Epub September 1. doi: 10.1007 /s00420-020-01568-9.
  5. Zhou Q, Hu X, Zhou J, et al. Human papillomavirus DNA in surgical smoke during cervical loop electrosurgical excision procedures and its impact on the surgeon. Cancer Manag Res. 2019;11:3643-3654.
  6. Rioux M, Garland A, Webster D, et al. HPV-positive tonsillar cancer in two laser surgeons: case reports. J Otolaryngol Head Neck Surg. 2013;42:54-57.
  7. Hallmo P, Naess O. Laryngeal papillomatosis with human papillomavirus DNA contracted by a laser surgeon. Eur Arch Otorhinolaryngol. 1991;248:425-427.
  8. Stockdale CK, Einstein MH, Huh WK. ASCCP recommends HPV vaccination for providers. February 19, 2020. www.asccp.org/Assets/d3abdb05-25c5-4e58-%209cec-05c11fb2b920/637177876310030000/hpv-vaccinemember-announcment-02-19-20-pdf. Accessed October 23, 2020.

  9. Harrison R, Huh W. Occupational exposure to human papillomavirus and vaccination for health care workers. Obstet Gynecol. 2020;136:663-665

 

 

Surprisingly, in the United States, the most common cancer associated with human papillomavirus (HPV) is oropharyngeal squamous cell cancer (SCC), with one study reporting 15,479 cases among men and 3,428 cases among women in 2015.1 In the same year, the investigators reported 11,788 cases of cervical cancer.1 A public health concern is that cases of oropharyngeal SCC are increasing, while cases of cervical cancer are decreasing. From 1999 to 2015, the rate of oropharyngeal SCC increased annually among both men and women, at rates of 2.7% and 0.8% per year, respectively. By contrast, the rate of cervical cancer decreased by 1.6% per year.1

Although the incidence of HPV-negative oropharyngeal SCC (cases associated with cigarette smoking) has declined by 50% from 1988 to 2004, the incidence of HPV-positive oropharyngeal SCC has increased by 225%, with much of the increase occurring among young, white men.2 HPV infection is a major cause of oropharyngeal SCC at the base of the tongue and tonsils, but not in the soft palate or oropharyngeal walls.3

Most physicians and parents recognize that the 9-valent (9v)HPV vaccine prevents the majority of cervical cancers and precancers in women. Far fewer people realize that there is an important opportunity to prevent a large number of oropharyngeal cancers by improving 9vHPV vaccination in men and women.

Which HPV types are associated with oropharyngeal cancer?

HPV16 is the most common HPV type associated with oropharyngeal SCC. Among these cancer types, greater than 80% harbor HPV16, with greater than 90% harboring HPV16 or 18 and less than 10% of tumors associated with HPV types 31, 33, 45, 52, or 58.4-7

The high prevalence of HPV16 in patients with oropharyngeal cancer raises the question of the HPV status of the intimate partner of the index patient. In one study of 164 people with HPV detected in their oropharyngeal, the partner of the index patient had a low prevalence of high-risk HPV types (1.2%) in oral rinse and gargle samples, similar to the rate in the general population (1.3%).7 This finding is reassuring and suggests that intimate partners of patients with HPV-positive oropharyngeal cancer effectively clear high-risk HPV virus from the oropharynx. The HPV status of the genital tissue of the intimate partner of an index patient with oropharyngeal SCC has not been adequately studied.

Men are more likely than women to harbor oral HPV

Among a sample of 5,501 men and women aged 14 to 69 years from the National Health and Nutrition Examination Survey, oral rinses were obtained and analyzed for the presence of HPV.8 The prevalence of any oral HPV and any oral high-risk HPV was 6.9% and 3.7%, respectively. Oral HPV-16 was detected in 1.6% of men and 0.3% of women. The prevalence of HPV was higher among current smokers, heavy alcohol drinkers, and people with a history of a greater number of sexual partners. In men and women reporting more than 20 lifetime sexual partners, the prevalence of oral HPV was 20%.

In a study of 2,627 men and women aged 18 to 33 years, the prevalence of oral HPV 16/18/6/11 was lower among those vaccinated versus those unvaccinated (0.11% and 1.6%, respectively; P = .008).9 Among men, oral HPV 16/18/6/11 was lower among those vaccinated versus unvaccinated (0.0% and 2.13%, respectively; P = .007).9 The results of this observational study support the important role of vaccination in reducing oral HPV infection.

9vHPV vaccine: Indications and immunization schedule

In 2020, the US Food and Drug Administration (FDA) approved the 9-valent human papillomavirus (9vHPV) vaccine for the prevention of oropharyngeal cancer. The 9vHPV vaccine contains inactive L1 capsid proteins for 9 HPV types, including types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The vaccine stimulates the production of neutralizing antibodies to the capsid protein.

9vHPV is approved for females aged 9 to 45 years to prevent cancers and precancers of the cervix, vulva, vagina, and anus caused by HPV types 16, 18, 31, 33, 45, 52, and 58.1 It is also approved for males aged 9 to 45 years to prevent cancer and precancers of the anus caused by those viral types. In 2020 the 9vHPV vaccine was approved by the FDA to prevent oropharyngeal cancer in males and females. Of note, the FDA reported that, “the oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”2

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of girls and boys, 11 to 12 years of age.1 Children with a history of sexual abuse or assault can start the vaccine at 9 years of age. Catch-up vaccination is recommended for all females and males through age 26 years. The ACIP recommends shared clinical decision-making regarding vaccination for some adults 27 to 45 years of age. Gynecologists with routine exposure to HPV may have occupational risk that warrants HPV vaccination3 (see “As a gynecologist, should you receive the 9vHPV vaccine?”).

For most individuals who start the vaccine series before age 15, two doses of 9vHPV vaccine are recommended, with the second dose 6 to 12 months following the first dose. For teens and adults aged 15 to 26 years, 3 doses of 9vHPV vaccine are recommended, with the second dose 1 to 2 months later and the third dose 6 months following the first dose. Immunocompromised individuals 9 to 26 years of age, including those with HIV infection, should receive 3 doses of the vaccine.

References

1. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.

2. Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck & Co. Inc; 2020.

3. Stockdale CK, Einstein MH, Huh WK. ASCCP recommends HPV vaccination for providers. February 19, 2020. https://www.asccp.org/Assets/d3abdb05-25c5-4e58-9cec-05c11fb2b920/637177876310030000/hpv-vaccinemember-announcment-02-19-20-pdf. Accessed October 23, 2020.

Continue to: Vaccinate boys and girls to prevent cancer...

 

 

Vaccinate boys and girls to prevent cancer

Most population studies report that males are less likely to receive an HPV vaccine than females. For example, based on the National Health Interview Survey of people aged 18 to 26, the percentage of women who self-reported receiving at least one dose of HPV vaccine was 37% in 2013 and 54% in 2018.10 By contrast, among men, the rates of self-reported vaccination were much lower—8% in 2013 and 27% in 2018.10

The percentage of women who received the recommended number of doses of HPV vaccine (see “9vHPV vaccine: Indications and immunization schedule”) was 26% in 2013 and 35% in 2018.10 For men, these percentages were 2% in 2013 and 9% in 2018.10 These data indicate that, compared with women, men are less likely to receive an HPV vaccination and far less likely to have received the recommended number of doses.

It is heartening that there has been a slow and steady increase in the prevalence of HPV vaccination. In fact, increasing the HPV vaccination rate among both boys and girls has the potential to markedly reduce the incidence of oropharyngeal cancer.

The reasons for the female-male gap in vaccination rates are not fully characterized. For one, parental awareness of the importance of HPV vaccination to prevent cancer among men is limited, and represents an important opportunity for additional public health education. In a qualitative interview study of mothers with children aged 11 to 19, the investigators reported that most mothers were aware that HPV vaccination could prevent cervical cancer in women, but most mothers did not know that HPV causes cancer of the mouth and that vaccination could prevent oropharyngeal cancer in boys and girls.11 Because of this lack of knowledge, the mothers did not think their sons needed to have an HPV vaccine. The research report is aptly titled, “I don’t think he needs the HPV vaccine cause boys can’t have cervical cancer.”11

Clinicians are highly influential in guiding parents to accept HPV vaccination of their children. Offering consistent messaging to parents that HPV vaccination prevents cancer in both women and men, and reducing the out-of-pocket cost of vaccination surely will result in an increase in the vaccination rate of boys and girls. ●

As a gynecologist, should you receive the 9vHPV vaccine?

Surgical treatment of tissues infected with human papillomavirus (HPV) often involves the use of laser or electrosurgical devices that generate smoke, which is known to contain HPV nucleic acid sequences and may contain infective virions.1 It is known that HPV nucleic acid sequences are present in surgical smoke. In one study plantar warts were treated with a carbon dioxide laser or electrocoagulation. The vapor produced from the surgery was collected with a dry filter apparatus. Five of 8 laser-derived vapors and 4 of 7 electrocoagulation-derived vapors were positive for HPV DNA. The concentration of HPV DNA was greater with laser than with electrocoagulation treatment.2

It is not known if surgical smoke derived from treatment of HPV-infected tissues contains infective HPV virions. In an experimental bovine model, smoke generated by laser ablation of fibropapillomas was collected. Injection of the contents of the smoke caused cutaneous papillomavirus lesions when inoculated into calves, suggesting that the smoke contained infective HPV virions.3 Although this animal experiment is a proof of principle that surgical smoke generated from treatment of HPVinfected tissue contain virions, it is unclear if surgical smoke generated in gynecologic practice contains HPV virions.

To investigate the prevalence of nasal HPV DNA among gynecologists, 700 physicians in Zhejiang Province, China, completed a questionnaire and provided a nasal swab for HPV DNA analysis.4 Among gynecologists who performed or did not perform LEEP, the prevalence of HPV DNA in the nose was 10% and 3%, respectively. The most common HPV types detected were HPV16 (76%), HPV31 (10%), HPV58 (5%), HPV55 (5%), HPV56 (2%), and HPV59 (2%).4 Among gynecologists who performed LEEP procedures, the prevalence of HPV DNA was 19% for those who did not use a surgical mask, 8% for clinicians who used a standard surgical mask, and 0% for those who used an N95 filtering facepiece respirator, suggesting that an N95 respirator provides the greatest protection from surgical smoke.4 Over 24 months of follow-up, all the gynecologists who had initially tested positive for HPV DNA no longer had detectable nasal HPV DNA. In this study, no gynecologist was diagnosed with an HPV-associated oropharyngeal disease. The investigators concluded that surgical masks, especially an N95 respirator, should be used by gynecologists performing LEEP procedures.

Investigators also have evaluated for the presence of HPV DNA in matched samples from the cervix of 134 patients undergoing loop electrosurgical excision procedure (LEEP) for cervical dysplasia, as well as the smoke generated during the procedure and nasal swabs from the surgeon performing the LEEP.5 HPV DNA was detected in 95% of the cervical samples, 30% of the surgical smoke samples, and 1.5% of the surgeons’ nasal swabs.5 At 6 months of follow-up, the two surgeons who initially had HPV-positive nasal swabs no longer had detected HPV DNA.

Of concern is that otolaryngologists have reported sporadic cases of oropharyngeal squamous cell cancer6 and laryngeal papillomatosis7 in health care workers with frequent and repetitive exposure to HPVs. For example, in one case report, a 53-year-old male gynecologist, nonsmoker, presented to his physician with a lump on the neck.6 The gynecologist had performed more than 3,000 laser ablation or LEEP procedures of dysplastic cervical, vaginal, and vulvar lesions over a span of 20 years.6 Most of the procedures were performed without wearing a mask and in a poorly ventilated procedure room. A computed tomography scan demonstrated a 2.2-cm soft tissue lesion in the right tonsil extending to the right soft palate and a level-2 lymph node. A biopsy of the tonsil confirmed invasive squamous cell carcinoma containing HPV16. He was treated with 35 fractions of radiotherapy and adjuvant cisplatin. Treatment adverse effects included dysphagia and xerostomia, and the patient lost 40 pounds.

Available interventions to reduce exposure of clinicians to HPV virions that may be present in surgical smoke include:

  • wearing a fit-tested N95 respirator  
  • routinely using a smoke evacuation device, and
  • ensuring sufficient ventilation in the procedure room.

A new recommendation is to consider 9vHPV vaccination for clinicians who are routinely exposed to HPV virions.8,9 In February 2020, the American Society for Colposcopy and Cervical Pathology recommended that clinicians who are routinely exposed to HPVs consider 9vHPV vaccination.8 This recommendation pertains to all members of the clinical team in the procedure room, including physicians, nurses, and staff. Based on the available data, gynecologists who have not been vaccinated will need to weigh the benefits and costs of receiving a 9vHPV vaccine to protect themselves against an occupational exposure that may adversely impact their health.

References

  1. Liu Y, Song Y, Hu X, et al. Awareness of surgical smoke hazards and enhancement of surgical smoke prevention among gynecologists. J Cancer. 2019;10:2788-2799.
  2. Sawchuk WS, Weber PJ, Lowy DR, et al. Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: detection and protection. J Am Acad Dermatol. 1989;21:41-49.
  3. Garden JM, O’Banion MK, Bakus AD, et al. Viral transmitted by laser-generated plume (aerosol). Arch Dermatol. 2002;138:1303-1307.
  4. Hu X, Zhou Q, Yu J, et al. Prevalence of HPV infections in surgical smoke exposed gynecologists. Int Arch Occup Environ Health. 2020; Epub September 1. doi: 10.1007 /s00420-020-01568-9.
  5. Zhou Q, Hu X, Zhou J, et al. Human papillomavirus DNA in surgical smoke during cervical loop electrosurgical excision procedures and its impact on the surgeon. Cancer Manag Res. 2019;11:3643-3654.
  6. Rioux M, Garland A, Webster D, et al. HPV-positive tonsillar cancer in two laser surgeons: case reports. J Otolaryngol Head Neck Surg. 2013;42:54-57.
  7. Hallmo P, Naess O. Laryngeal papillomatosis with human papillomavirus DNA contracted by a laser surgeon. Eur Arch Otorhinolaryngol. 1991;248:425-427.
  8. Stockdale CK, Einstein MH, Huh WK. ASCCP recommends HPV vaccination for providers. February 19, 2020. www.asccp.org/Assets/d3abdb05-25c5-4e58-%209cec-05c11fb2b920/637177876310030000/hpv-vaccinemember-announcment-02-19-20-pdf. Accessed October 23, 2020.

  9. Harrison R, Huh W. Occupational exposure to human papillomavirus and vaccination for health care workers. Obstet Gynecol. 2020;136:663-665

 

 

References
  1. Van Dyne EA, Henley SJ, Saraiya M, et al. Trends in human papillomavirus-associated cancers--United States, 1999-2015. MMWR. 2018;67:918-924. 
  2. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294-4301. 
  3. Haeggblom L, Ramqvist T, Tommasino M, et al. Time to change perspective on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years. Papillomavirus Research. 2017;4:1-11. 
  4. Kreimer AR, Clifford GM, Boyle P, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467-475.  
  5. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944-1956. 
  6. de Martel C, Plummer M, Vignat J, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141:664-670. 
  7. D'Souza G, Gross ND, Pai SI, et al. Oral human papillomavirus infection in HPV-positive patients with oropharyngeal cancer and their partners. J Clin Oncol. 2014;32:2408-2415. 
  8. Gillison ML, Broutian T, Pickard RK, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307:693. 
  9. Chaturvedi AK, Graubard BI, Broutian T, et al. Effect of prophylactic human papillomavirus vaccination on oral HPV infections among young adults in the United States. J Clin Oncol. 2018;36:262-267. 
  10. Boersma P, Black LI. Human papillomavirus vaccination among adults aged 18 to 26, 2013-2018. NCHS Data Brief. 2020:1-8. 
  11. Lindsay AC, Delgado D, Valdez MJ, et al. "I don't think he needs the HPV vaccine cause boys can't have cervical cancer": a qualitative study of Latina mothers' (Mis) understandings about human papillomavirus transmission, associated cancers and the vaccine. J Cancer Educ. July 11, 2020. doi: 10.1007/s13187-020-01824-z.
References
  1. Van Dyne EA, Henley SJ, Saraiya M, et al. Trends in human papillomavirus-associated cancers--United States, 1999-2015. MMWR. 2018;67:918-924. 
  2. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294-4301. 
  3. Haeggblom L, Ramqvist T, Tommasino M, et al. Time to change perspective on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years. Papillomavirus Research. 2017;4:1-11. 
  4. Kreimer AR, Clifford GM, Boyle P, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467-475.  
  5. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944-1956. 
  6. de Martel C, Plummer M, Vignat J, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141:664-670. 
  7. D'Souza G, Gross ND, Pai SI, et al. Oral human papillomavirus infection in HPV-positive patients with oropharyngeal cancer and their partners. J Clin Oncol. 2014;32:2408-2415. 
  8. Gillison ML, Broutian T, Pickard RK, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307:693. 
  9. Chaturvedi AK, Graubard BI, Broutian T, et al. Effect of prophylactic human papillomavirus vaccination on oral HPV infections among young adults in the United States. J Clin Oncol. 2018;36:262-267. 
  10. Boersma P, Black LI. Human papillomavirus vaccination among adults aged 18 to 26, 2013-2018. NCHS Data Brief. 2020:1-8. 
  11. Lindsay AC, Delgado D, Valdez MJ, et al. "I don't think he needs the HPV vaccine cause boys can't have cervical cancer": a qualitative study of Latina mothers' (Mis) understandings about human papillomavirus transmission, associated cancers and the vaccine. J Cancer Educ. July 11, 2020. doi: 10.1007/s13187-020-01824-z.
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