Sexual Health

Although vaccination rates against the human papillomavirus remain low for young adults across the United States, the number of self-reported HPV vaccinations among women and men aged between 18 and 21 years has markedly increased since 2010, according to new research findings.

The findings were published online April 27, 2021, as a research letter in JAMA.

In 2006, the Food and Drug Administration approved the HPV vaccine for the prevention of cervical cancer and genital warts in female patients. Three years later, the FDA approved the vaccine for the prevention of anogenital cancer and warts in male patients.

The Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention recommend two doses of the HPV vaccine for children aged 11-12 years. Adolescents and young adults may need three doses over the course of 6 months if they start their vaccine series on or following their 15th birthday.

For persons who have not previously received the HPV vaccine or who did not receive adequate doses, the HPV vaccine is recommended through age 26. Data on the rates of vaccination among young adults between 18 and 21 years of age in the United States are sparse, and it is not known how well vaccination programs are progressing in the country.

In the recently published JAMA research letter, investigators from the University of Michigan, Ann Arbor, examined data for the period 2010-2018 from the cross-sectional National Health Interview Survey. Respondents included in the analysis were aged 18-21 years. They were asked whether they had received the HPV vaccine before age 18 and at what age they had been vaccinated against the virus.

The researchers also assessed whether the respondents had received any HPV vaccine dose between the ages of 18 and 21 years. The findings were limited to self-reported vaccination status.

In total, 6,606 women and 6,038 men were included in the analysis. Approximately 42% of women and 16% of men said they had received at least one HPV vaccine dose at any age. The proportion of female patients who reported receiving an HPV vaccine dose significantly increased from 32% in 2010 to 55% in 2018 (P =.001). Similarly, among men, the percentage significantly increased from 2% in 2010 to 34% in 2018 (P <.001).

Approximately 4% of the female respondents and 3% of the male respondents reported that they had received an HPV vaccine between the ages of 18 and 21 years; 46% of women and 29% of men who received the vaccine between these ages completed the recommended vaccination series.

Findings from the study highlight the continual need for improving vaccination rates among vulnerable populations. Lead study author Michelle Chen, MD, MHS, a professor in the department of otolaryngology–head and neck surgery at the University of Michigan, explained in an interview that there are multiple barriers to HPV vaccination among young adults. “These barriers to vaccination among young adults primarily include cost, lack of knowledge and awareness, missed opportunities for vaccination, rapidly changing guidelines, and initial gender-based guidelines,” said Dr. Chen.

Clinicians play a large role in improving vaccination rates among young adults, who may lack awareness of the overall importance of inoculation against the potentially debilitating and deadly virus. Dr. Chen noted that clinicians can lead the way by increasing gender-inclusive awareness of HPV-associated diseases and HPV vaccination, by performing routine vaccine eligibility assessments for young adults regardless of sex, by developing robust reminder and recall strategies to improve series completion rates, and by offering patients resources regarding assistance programs to address cost barriers for uninsured patients.

“Young adult men are particularly vulnerable [to HPV], because they start to age out of pediatric health practices,” added Dr. Chen. “Thus, a multilevel gender-inclusive approach is needed to target clinicians, patients, parents, and community-based organizations.”

Gypsyamber D’Souza, PhD, professor of epidemiology at Johns Hopkins University, Baltimore, said in an interview that the initial uptake of HPV vaccination was slow in the United States but that progress has been made in recent years among persons in the targeted age range of 11-12 years. “However, catch-up vaccination has lagged behind, and sadly, we’re still seeing low uptake in those older ages that are still eligible and where we know there still is tremendous benefit,” she said.

Dr. D’Souza is a lead investigator in the MOUTH trial, which is currently enrolling patients. That trial will examine potential biomarkers for oropharyngeal cancer risk among people with known risk factors for HPV who came of age prior to the rollout of the vaccine.

She explained that many parents want their children to be vaccinated for HPV after they hear about the vaccine, but because the health care system in the United States is an “opt-in” system, rather than an “opt-out” one, parents need to actively seek out vaccination. Children then move toward adulthood without having received the recommended vaccine course. “There are individuals who did not get vaccinated at the ages of 11 and 12 and then forget to ask about it later, or the provider asks about it and the patients don’t have enough information,” Dr. D’Souza said.

She noted that one reason why HPV vaccination rates remain low among young adults is that the vaccine is not often kept in stock other than in pediatric clinics. “Because vaccines expire and clinics don’t have a lot of people in that age group getting vaccinated, they may not have it regularly in stock, making this one reason it might be hard for someone to get vaccinated.”

The HPV vaccine is not effective for clearing HPV once a patient acquires the infection, she added. “So young adulthood is a critical time where we have individuals who still can benefit from being vaccinated, but if we wait too long, they’ll age out of those ages where we see the highest efficacy.”

Ultimately, said Dr. D’Souza, clinicians need to catch people at multiple time points and work to remove barriers to vaccination, including letting patients know that HPV vaccination is covered by insurance. “There’s a lot of opportunity to prevent future cancers in young adults by having care providers for that age group talk about the vaccine and remember to offer it.”

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

Although vaccination rates against the human papillomavirus remain low for young adults across the United States, the number of self-reported HPV vaccinations among women and men aged between 18 and 21 years has markedly increased since 2010, according to new research findings.

The findings were published online April 27, 2021, as a research letter in JAMA.

In 2006, the Food and Drug Administration approved the HPV vaccine for the prevention of cervical cancer and genital warts in female patients. Three years later, the FDA approved the vaccine for the prevention of anogenital cancer and warts in male patients.

The Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention recommend two doses of the HPV vaccine for children aged 11-12 years. Adolescents and young adults may need three doses over the course of 6 months if they start their vaccine series on or following their 15th birthday.

For persons who have not previously received the HPV vaccine or who did not receive adequate doses, the HPV vaccine is recommended through age 26. Data on the rates of vaccination among young adults between 18 and 21 years of age in the United States are sparse, and it is not known how well vaccination programs are progressing in the country.

In the recently published JAMA research letter, investigators from the University of Michigan, Ann Arbor, examined data for the period 2010-2018 from the cross-sectional National Health Interview Survey. Respondents included in the analysis were aged 18-21 years. They were asked whether they had received the HPV vaccine before age 18 and at what age they had been vaccinated against the virus.

The researchers also assessed whether the respondents had received any HPV vaccine dose between the ages of 18 and 21 years. The findings were limited to self-reported vaccination status.

In total, 6,606 women and 6,038 men were included in the analysis. Approximately 42% of women and 16% of men said they had received at least one HPV vaccine dose at any age. The proportion of female patients who reported receiving an HPV vaccine dose significantly increased from 32% in 2010 to 55% in 2018 (P =.001). Similarly, among men, the percentage significantly increased from 2% in 2010 to 34% in 2018 (P <.001).

Approximately 4% of the female respondents and 3% of the male respondents reported that they had received an HPV vaccine between the ages of 18 and 21 years; 46% of women and 29% of men who received the vaccine between these ages completed the recommended vaccination series.

Findings from the study highlight the continual need for improving vaccination rates among vulnerable populations. Lead study author Michelle Chen, MD, MHS, a professor in the department of otolaryngology–head and neck surgery at the University of Michigan, explained in an interview that there are multiple barriers to HPV vaccination among young adults. “These barriers to vaccination among young adults primarily include cost, lack of knowledge and awareness, missed opportunities for vaccination, rapidly changing guidelines, and initial gender-based guidelines,” said Dr. Chen.

Clinicians play a large role in improving vaccination rates among young adults, who may lack awareness of the overall importance of inoculation against the potentially debilitating and deadly virus. Dr. Chen noted that clinicians can lead the way by increasing gender-inclusive awareness of HPV-associated diseases and HPV vaccination, by performing routine vaccine eligibility assessments for young adults regardless of sex, by developing robust reminder and recall strategies to improve series completion rates, and by offering patients resources regarding assistance programs to address cost barriers for uninsured patients.

“Young adult men are particularly vulnerable [to HPV], because they start to age out of pediatric health practices,” added Dr. Chen. “Thus, a multilevel gender-inclusive approach is needed to target clinicians, patients, parents, and community-based organizations.”

Gypsyamber D’Souza, PhD, professor of epidemiology at Johns Hopkins University, Baltimore, said in an interview that the initial uptake of HPV vaccination was slow in the United States but that progress has been made in recent years among persons in the targeted age range of 11-12 years. “However, catch-up vaccination has lagged behind, and sadly, we’re still seeing low uptake in those older ages that are still eligible and where we know there still is tremendous benefit,” she said.

Dr. D’Souza is a lead investigator in the MOUTH trial, which is currently enrolling patients. That trial will examine potential biomarkers for oropharyngeal cancer risk among people with known risk factors for HPV who came of age prior to the rollout of the vaccine.

She explained that many parents want their children to be vaccinated for HPV after they hear about the vaccine, but because the health care system in the United States is an “opt-in” system, rather than an “opt-out” one, parents need to actively seek out vaccination. Children then move toward adulthood without having received the recommended vaccine course. “There are individuals who did not get vaccinated at the ages of 11 and 12 and then forget to ask about it later, or the provider asks about it and the patients don’t have enough information,” Dr. D’Souza said.

She noted that one reason why HPV vaccination rates remain low among young adults is that the vaccine is not often kept in stock other than in pediatric clinics. “Because vaccines expire and clinics don’t have a lot of people in that age group getting vaccinated, they may not have it regularly in stock, making this one reason it might be hard for someone to get vaccinated.”

The HPV vaccine is not effective for clearing HPV once a patient acquires the infection, she added. “So young adulthood is a critical time where we have individuals who still can benefit from being vaccinated, but if we wait too long, they’ll age out of those ages where we see the highest efficacy.”

Ultimately, said Dr. D’Souza, clinicians need to catch people at multiple time points and work to remove barriers to vaccination, including letting patients know that HPV vaccination is covered by insurance. “There’s a lot of opportunity to prevent future cancers in young adults by having care providers for that age group talk about the vaccine and remember to offer it.”

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

Although vaccination rates against the human papillomavirus remain low for young adults across the United States, the number of self-reported HPV vaccinations among women and men aged between 18 and 21 years has markedly increased since 2010, according to new research findings.

The findings were published online April 27, 2021, as a research letter in JAMA.

In 2006, the Food and Drug Administration approved the HPV vaccine for the prevention of cervical cancer and genital warts in female patients. Three years later, the FDA approved the vaccine for the prevention of anogenital cancer and warts in male patients.

The Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention recommend two doses of the HPV vaccine for children aged 11-12 years. Adolescents and young adults may need three doses over the course of 6 months if they start their vaccine series on or following their 15th birthday.

For persons who have not previously received the HPV vaccine or who did not receive adequate doses, the HPV vaccine is recommended through age 26. Data on the rates of vaccination among young adults between 18 and 21 years of age in the United States are sparse, and it is not known how well vaccination programs are progressing in the country.

In the recently published JAMA research letter, investigators from the University of Michigan, Ann Arbor, examined data for the period 2010-2018 from the cross-sectional National Health Interview Survey. Respondents included in the analysis were aged 18-21 years. They were asked whether they had received the HPV vaccine before age 18 and at what age they had been vaccinated against the virus.

The researchers also assessed whether the respondents had received any HPV vaccine dose between the ages of 18 and 21 years. The findings were limited to self-reported vaccination status.

In total, 6,606 women and 6,038 men were included in the analysis. Approximately 42% of women and 16% of men said they had received at least one HPV vaccine dose at any age. The proportion of female patients who reported receiving an HPV vaccine dose significantly increased from 32% in 2010 to 55% in 2018 (P =.001). Similarly, among men, the percentage significantly increased from 2% in 2010 to 34% in 2018 (P <.001).

Approximately 4% of the female respondents and 3% of the male respondents reported that they had received an HPV vaccine between the ages of 18 and 21 years; 46% of women and 29% of men who received the vaccine between these ages completed the recommended vaccination series.

Findings from the study highlight the continual need for improving vaccination rates among vulnerable populations. Lead study author Michelle Chen, MD, MHS, a professor in the department of otolaryngology–head and neck surgery at the University of Michigan, explained in an interview that there are multiple barriers to HPV vaccination among young adults. “These barriers to vaccination among young adults primarily include cost, lack of knowledge and awareness, missed opportunities for vaccination, rapidly changing guidelines, and initial gender-based guidelines,” said Dr. Chen.

Clinicians play a large role in improving vaccination rates among young adults, who may lack awareness of the overall importance of inoculation against the potentially debilitating and deadly virus. Dr. Chen noted that clinicians can lead the way by increasing gender-inclusive awareness of HPV-associated diseases and HPV vaccination, by performing routine vaccine eligibility assessments for young adults regardless of sex, by developing robust reminder and recall strategies to improve series completion rates, and by offering patients resources regarding assistance programs to address cost barriers for uninsured patients.

“Young adult men are particularly vulnerable [to HPV], because they start to age out of pediatric health practices,” added Dr. Chen. “Thus, a multilevel gender-inclusive approach is needed to target clinicians, patients, parents, and community-based organizations.”

Gypsyamber D’Souza, PhD, professor of epidemiology at Johns Hopkins University, Baltimore, said in an interview that the initial uptake of HPV vaccination was slow in the United States but that progress has been made in recent years among persons in the targeted age range of 11-12 years. “However, catch-up vaccination has lagged behind, and sadly, we’re still seeing low uptake in those older ages that are still eligible and where we know there still is tremendous benefit,” she said.

Dr. D’Souza is a lead investigator in the MOUTH trial, which is currently enrolling patients. That trial will examine potential biomarkers for oropharyngeal cancer risk among people with known risk factors for HPV who came of age prior to the rollout of the vaccine.

She explained that many parents want their children to be vaccinated for HPV after they hear about the vaccine, but because the health care system in the United States is an “opt-in” system, rather than an “opt-out” one, parents need to actively seek out vaccination. Children then move toward adulthood without having received the recommended vaccine course. “There are individuals who did not get vaccinated at the ages of 11 and 12 and then forget to ask about it later, or the provider asks about it and the patients don’t have enough information,” Dr. D’Souza said.

She noted that one reason why HPV vaccination rates remain low among young adults is that the vaccine is not often kept in stock other than in pediatric clinics. “Because vaccines expire and clinics don’t have a lot of people in that age group getting vaccinated, they may not have it regularly in stock, making this one reason it might be hard for someone to get vaccinated.”

The HPV vaccine is not effective for clearing HPV once a patient acquires the infection, she added. “So young adulthood is a critical time where we have individuals who still can benefit from being vaccinated, but if we wait too long, they’ll age out of those ages where we see the highest efficacy.”

Ultimately, said Dr. D’Souza, clinicians need to catch people at multiple time points and work to remove barriers to vaccination, including letting patients know that HPV vaccination is covered by insurance. “There’s a lot of opportunity to prevent future cancers in young adults by having care providers for that age group talk about the vaccine and remember to offer it.”

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

On any given day in 2018, one in five people had a sexually transmitted infection (STI), according to the US Centers for Disease Control and Prevention’s (CDC) recently released Sexually Transmitted Disease (STD) Surveillance Report, 2018. There were nearly 68 million infections in the US—and 26 million STIs were acquired in that year.

                “The CDC report is an important reminder that infectious diseases continue to do what they do best, which is to cause illness and spread from person to person,” says David Aronoff, MD, director, Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center. “Sexually transmitted infections are persistent threats to human health.”

                Most of the infections on the CDC’s watchlist were due to the human papillomavirus (HPV), herpes simplex virus-2 (HSV-2), and trichomoniasis. Chlamydia, gonorrhea, HIV, hepatitis B virus, and syphilis followed. Although lower on the list, gonorrhea and syphilis numbers are on the rise to a disquieting degree. Since 2014, gonorrhea cases have increased 63% and syphilis cases, 71%.

                Syphilis is still treatable with penicillin. But “the tragedy of poor STI [sexually transmitted infection] control is compounded by the fact that many of the germs that cause STIs are gradually developing more and more resistance to available treatments,” Dr. Aronoff says.

                The rise in gonorrhea cases is particularly concerning to many health care providers. “There’s a very limited pipeline of new antibiotics to use if we’re confronted with antibiotic-resistant STIs,” says Ina Park, MD, assistant professor at University of California San Francisco School of Medicine; medical director, California Prevention Training Center; and author of Strange Bedfellows: Adventures in the Science, History and Surprising Secrets of STDs. In the case of gonorrhea, she warns, we’re down to one class of antibiotics. When all conventional therapies fail in cases of multidrug-resistant gonorrhea, patients have to be hospitalized and treated with broad-spectrum IV antibiotics, such as ertapenem. “We really don’t want to have to resort to that for an infection as common as gonorrhea,” she says.

                Syphilis’ resurgence in new populations also is a concern. In the ’80s, says Michelle Collins-Ogle, MD, there was an epidemic of syphilis in pregnant women and newborns. Then it “sort of quieted down,” she says, in part because obstetricians and gynecologists and other health care providers did a better job of screening, diagnosing, and treating in that demographic. The latest resurgence is in young men of color who have sex with men—“we didn’t see that coming.”

                Women and babies are still vulnerable, though. In one year, according to the CDC, syphilis cases among women of childbearing age leaped 36%. And, alarmingly, since 2014, cases of congenital syphilis have increased 185%. Between 2017 and 2018 alone, newborn deaths due to syphilis increased 22%—a “startling” number, says Gail Bolan, MD, the CDC director of STD prevention, in a release about the surveillance report. “Too many babies are needlessly dying. Every single instance of congenital syphilis is one too many when we have the tools to prevent it.”

                Can all STIs be prevented? Can the rising tides be turned? Dr. Aronoff says, “As with the COVID-19 pandemic, STIs provide an important opportunity for us to understand how multiple factors can contribute to their spread and difficulty controlling.” Drug use, poverty, unstable housing, and stigma can all reduce access to STD prevention and care, he says. “And, as we’ve seen with COVID-19, under-resourced public health programs can also foster epidemics and pandemics of STIs.” Moreover, he adds, many public health programs at the state and local level have been subjected to budget cuts, which translates into less control of disease.

                Some STI rates have been reduced with, for instance, antiretrovirals for HIV/AIDS and the HPV vaccine. But there’s still ground to cover, and new patient groups to protect. Nearly half of all new infections in 2018 were in young people aged 15 to 24 years. Not only is it another dangerous trend, it is an expensive one. Chlamydia, gonorrhea, and syphilis combined accounted for $1.1 billion in direct medical costs in 2018, the CDC report says, and care for young people aged 15 to 24 made up about 60% of those costs.

                “Low or decreasing rates of condom use among vulnerable groups, including young people and gay and bisexual men, play important roles in driving ongoing STI rates,” Aronoff says. In part, that’s due to lack of comprehensive sex education, a lack that’s taking a huge toll.

                “Remember now, we basically cut out a lot of the sex education. It doesn’t exist,” says Dr. Collins-Ogle. She has run clinics for several decades, and says she continually sees young male patients who don’t know how to use a condom. We know more now, though, she points out. “Back in the ‘80s, we didn’t have a direct correlation between STIs and AIDS. Now we know that having syphilis, for example, predisposes you to HIV acquisition. We also know that having HSV2, for example, predisposes you to HIV.”

                It’s an ongoing battle, though, with each new generation of pathogens—and people. And as the CDC report shows, it’s like fighting a Hydra: When one infection is wrestled to the ground, another rears its head. There’s no time to rest on laurels. “Having highly contagious infections caused by difficult or impossible-to-treat microbes,” says David Aronoff, “is not a future I would wish on anyone

On any given day in 2018, one in five people had a sexually transmitted infection (STI), according to the US Centers for Disease Control and Prevention’s (CDC) recently released Sexually Transmitted Disease (STD) Surveillance Report, 2018. There were nearly 68 million infections in the US—and 26 million STIs were acquired in that year.

                “The CDC report is an important reminder that infectious diseases continue to do what they do best, which is to cause illness and spread from person to person,” says David Aronoff, MD, director, Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center. “Sexually transmitted infections are persistent threats to human health.”

                Most of the infections on the CDC’s watchlist were due to the human papillomavirus (HPV), herpes simplex virus-2 (HSV-2), and trichomoniasis. Chlamydia, gonorrhea, HIV, hepatitis B virus, and syphilis followed. Although lower on the list, gonorrhea and syphilis numbers are on the rise to a disquieting degree. Since 2014, gonorrhea cases have increased 63% and syphilis cases, 71%.

                Syphilis is still treatable with penicillin. But “the tragedy of poor STI [sexually transmitted infection] control is compounded by the fact that many of the germs that cause STIs are gradually developing more and more resistance to available treatments,” Dr. Aronoff says.

                The rise in gonorrhea cases is particularly concerning to many health care providers. “There’s a very limited pipeline of new antibiotics to use if we’re confronted with antibiotic-resistant STIs,” says Ina Park, MD, assistant professor at University of California San Francisco School of Medicine; medical director, California Prevention Training Center; and author of Strange Bedfellows: Adventures in the Science, History and Surprising Secrets of STDs. In the case of gonorrhea, she warns, we’re down to one class of antibiotics. When all conventional therapies fail in cases of multidrug-resistant gonorrhea, patients have to be hospitalized and treated with broad-spectrum IV antibiotics, such as ertapenem. “We really don’t want to have to resort to that for an infection as common as gonorrhea,” she says.

                Syphilis’ resurgence in new populations also is a concern. In the ’80s, says Michelle Collins-Ogle, MD, there was an epidemic of syphilis in pregnant women and newborns. Then it “sort of quieted down,” she says, in part because obstetricians and gynecologists and other health care providers did a better job of screening, diagnosing, and treating in that demographic. The latest resurgence is in young men of color who have sex with men—“we didn’t see that coming.”

                Women and babies are still vulnerable, though. In one year, according to the CDC, syphilis cases among women of childbearing age leaped 36%. And, alarmingly, since 2014, cases of congenital syphilis have increased 185%. Between 2017 and 2018 alone, newborn deaths due to syphilis increased 22%—a “startling” number, says Gail Bolan, MD, the CDC director of STD prevention, in a release about the surveillance report. “Too many babies are needlessly dying. Every single instance of congenital syphilis is one too many when we have the tools to prevent it.”

                Can all STIs be prevented? Can the rising tides be turned? Dr. Aronoff says, “As with the COVID-19 pandemic, STIs provide an important opportunity for us to understand how multiple factors can contribute to their spread and difficulty controlling.” Drug use, poverty, unstable housing, and stigma can all reduce access to STD prevention and care, he says. “And, as we’ve seen with COVID-19, under-resourced public health programs can also foster epidemics and pandemics of STIs.” Moreover, he adds, many public health programs at the state and local level have been subjected to budget cuts, which translates into less control of disease.

                Some STI rates have been reduced with, for instance, antiretrovirals for HIV/AIDS and the HPV vaccine. But there’s still ground to cover, and new patient groups to protect. Nearly half of all new infections in 2018 were in young people aged 15 to 24 years. Not only is it another dangerous trend, it is an expensive one. Chlamydia, gonorrhea, and syphilis combined accounted for $1.1 billion in direct medical costs in 2018, the CDC report says, and care for young people aged 15 to 24 made up about 60% of those costs.

                “Low or decreasing rates of condom use among vulnerable groups, including young people and gay and bisexual men, play important roles in driving ongoing STI rates,” Aronoff says. In part, that’s due to lack of comprehensive sex education, a lack that’s taking a huge toll.

                “Remember now, we basically cut out a lot of the sex education. It doesn’t exist,” says Dr. Collins-Ogle. She has run clinics for several decades, and says she continually sees young male patients who don’t know how to use a condom. We know more now, though, she points out. “Back in the ‘80s, we didn’t have a direct correlation between STIs and AIDS. Now we know that having syphilis, for example, predisposes you to HIV acquisition. We also know that having HSV2, for example, predisposes you to HIV.”

                It’s an ongoing battle, though, with each new generation of pathogens—and people. And as the CDC report shows, it’s like fighting a Hydra: When one infection is wrestled to the ground, another rears its head. There’s no time to rest on laurels. “Having highly contagious infections caused by difficult or impossible-to-treat microbes,” says David Aronoff, “is not a future I would wish on anyone

On any given day in 2018, one in five people had a sexually transmitted infection (STI), according to the US Centers for Disease Control and Prevention’s (CDC) recently released Sexually Transmitted Disease (STD) Surveillance Report, 2018. There were nearly 68 million infections in the US—and 26 million STIs were acquired in that year.

                “The CDC report is an important reminder that infectious diseases continue to do what they do best, which is to cause illness and spread from person to person,” says David Aronoff, MD, director, Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center. “Sexually transmitted infections are persistent threats to human health.”

                Most of the infections on the CDC’s watchlist were due to the human papillomavirus (HPV), herpes simplex virus-2 (HSV-2), and trichomoniasis. Chlamydia, gonorrhea, HIV, hepatitis B virus, and syphilis followed. Although lower on the list, gonorrhea and syphilis numbers are on the rise to a disquieting degree. Since 2014, gonorrhea cases have increased 63% and syphilis cases, 71%.

                Syphilis is still treatable with penicillin. But “the tragedy of poor STI [sexually transmitted infection] control is compounded by the fact that many of the germs that cause STIs are gradually developing more and more resistance to available treatments,” Dr. Aronoff says.

                The rise in gonorrhea cases is particularly concerning to many health care providers. “There’s a very limited pipeline of new antibiotics to use if we’re confronted with antibiotic-resistant STIs,” says Ina Park, MD, assistant professor at University of California San Francisco School of Medicine; medical director, California Prevention Training Center; and author of Strange Bedfellows: Adventures in the Science, History and Surprising Secrets of STDs. In the case of gonorrhea, she warns, we’re down to one class of antibiotics. When all conventional therapies fail in cases of multidrug-resistant gonorrhea, patients have to be hospitalized and treated with broad-spectrum IV antibiotics, such as ertapenem. “We really don’t want to have to resort to that for an infection as common as gonorrhea,” she says.

                Syphilis’ resurgence in new populations also is a concern. In the ’80s, says Michelle Collins-Ogle, MD, there was an epidemic of syphilis in pregnant women and newborns. Then it “sort of quieted down,” she says, in part because obstetricians and gynecologists and other health care providers did a better job of screening, diagnosing, and treating in that demographic. The latest resurgence is in young men of color who have sex with men—“we didn’t see that coming.”

                Women and babies are still vulnerable, though. In one year, according to the CDC, syphilis cases among women of childbearing age leaped 36%. And, alarmingly, since 2014, cases of congenital syphilis have increased 185%. Between 2017 and 2018 alone, newborn deaths due to syphilis increased 22%—a “startling” number, says Gail Bolan, MD, the CDC director of STD prevention, in a release about the surveillance report. “Too many babies are needlessly dying. Every single instance of congenital syphilis is one too many when we have the tools to prevent it.”

                Can all STIs be prevented? Can the rising tides be turned? Dr. Aronoff says, “As with the COVID-19 pandemic, STIs provide an important opportunity for us to understand how multiple factors can contribute to their spread and difficulty controlling.” Drug use, poverty, unstable housing, and stigma can all reduce access to STD prevention and care, he says. “And, as we’ve seen with COVID-19, under-resourced public health programs can also foster epidemics and pandemics of STIs.” Moreover, he adds, many public health programs at the state and local level have been subjected to budget cuts, which translates into less control of disease.

                Some STI rates have been reduced with, for instance, antiretrovirals for HIV/AIDS and the HPV vaccine. But there’s still ground to cover, and new patient groups to protect. Nearly half of all new infections in 2018 were in young people aged 15 to 24 years. Not only is it another dangerous trend, it is an expensive one. Chlamydia, gonorrhea, and syphilis combined accounted for $1.1 billion in direct medical costs in 2018, the CDC report says, and care for young people aged 15 to 24 made up about 60% of those costs.

                “Low or decreasing rates of condom use among vulnerable groups, including young people and gay and bisexual men, play important roles in driving ongoing STI rates,” Aronoff says. In part, that’s due to lack of comprehensive sex education, a lack that’s taking a huge toll.

                “Remember now, we basically cut out a lot of the sex education. It doesn’t exist,” says Dr. Collins-Ogle. She has run clinics for several decades, and says she continually sees young male patients who don’t know how to use a condom. We know more now, though, she points out. “Back in the ‘80s, we didn’t have a direct correlation between STIs and AIDS. Now we know that having syphilis, for example, predisposes you to HIV acquisition. We also know that having HSV2, for example, predisposes you to HIV.”

                It’s an ongoing battle, though, with each new generation of pathogens—and people. And as the CDC report shows, it’s like fighting a Hydra: When one infection is wrestled to the ground, another rears its head. There’s no time to rest on laurels. “Having highly contagious infections caused by difficult or impossible-to-treat microbes,” says David Aronoff, “is not a future I would wish on anyone

Testosterone treatment is clinically indicated when a patient presents with symptoms and signs and biochemical evidence of testosterone deficiency, ie, male hypogonadism. Laboratory confirmation of hypogonadism requires repeatedly low serum testosterone concentrations; between 8 am and 10 am on ≥ 2 separate occasions, and evaluation should include measurement of gonadotropin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) concentrations. If the diagnosis of hypogonadism is established, it is important to determine whether the etiology is due to a structural or congenital disorder of the hypothalamic-pituitary-testicular (HPT) axis (organic hypogonadism) or a comorbid condition that results in suppressed function of an intact HPT axis and that is potentially reversible or treatable (functional hypogonadism).^1,2 Prior to initiation of treatment, clinicians should discuss potential benefits and risks of testosterone and monitoring during treatment, using a shared decision-making process with the patient.¹

Recent studies have reported an increase in testosterone prescriptions and raised concerns regarding health care provider (HCP) prescribing practices despite current clinical practice guidelines from major societies, such as the Endocrine Society. In the US from 2001 to 2011, testosterone use among men aged ≥ 40 years increased more than 3-fold in all age groups.³ Subsequently in the years from 2013 to 2016, prescription rates declined perhaps due to the cardiovascular and stroke concerns.⁴

In the US Department of Veterans Affairs (VA), new testosterone prescriptions across VA medical centers increased from 20,437 in fiscal year (FY) 2009 to 36,394 in FY 2012. Yet only 3.1% of men who received testosterone therapy had 2 or more low morning total or free testosterone concentrations measured; LH and/or FSH levels assessed; and presence of contraindications to therapy documented. Remarkably, 16.5% of these veterans did not have a testosterone level tested prior to being prescribed testosterone. Among veterans who were prescribed testosterone, 1.4% had a diagnosis of prostate cancer, 7.6% had a diagnosis of obstructive sleep apnea (OSA), and 3.5% had elevated hematocrit at baseline.⁵ These findings raised concerns of whether the diagnosis and etiology of hypogonadism were appropriately established and risks were considered before testosterone treatment was initiated.^5,6

To further understand VA prescribing practices of testosterone therapy, a 2018 VA Office of the Inspector General (OIG) report evaluated the initiation and follow-up of testosterone replacement therapy. The OIG randomly sampled and reviewed 1,091 male patients who filled at least 1 outpatient testosterone prescription from VA in FY 2014 and who did not have a prior testosterone prescription in FY 2013. Patients were followed through September 30, 2015. Within 1 year prior to initiating testosterone, only 1.5% had clinical signs and symptoms of testosterone deficiency documented prior to testosterone testing (76% within 18 months of starting testosterone); only 9.1% of veterans had the recommended measurements of 2 low morning testosterone levels; and only 12% had LH and FSH levels measured. Within 3 to 6 months after starting testosterone therapy, only 24% of veterans were assessed for symptom improvement, and 29% to 33% were evaluated for adverse effects, hematocrit levels and adherence to the therapy. The OIG report concluded that VA HCPs were not adhering to guidelines (referencing the Endocrine Society guidelines) when evaluating and treating veterans with testosterone deficiency.⁷

Considering the OIG recommendations and need to improve current practices among providers, VA Puget Sound Health Care System (VAPSHCS) in Washington established a multidisciplinary workgroup consisting of an endocrinologist, geriatrician, primary care provider (PCP), pharmacists, VA information technology (IT) specialist, and health products support (HPS) clinical team in the spring of 2019 to assess and improve testosterone prescribing practices.

Methods

A testosterone order template was developed, approved by VAPSHCS Pharmacy and Therapeutics Committee, and implemented on July 1, 2019, at VAPSHCS, a 1a medical facility caring for more than 112,000 veterans. Given its potential risks and the propensity for varied prescribing practices, testosterone was designated as a restricted drug requiring a prior authorization drug request (PADR) and required completion of the testosterone order template in the Computerized Patient Record System (CPRS).

Testosterone Order Template

The testosterone order template had 2 components. Completion of the template for new testosterone orders was required to initiate treatment unless the patient had known organic hypogonadism or was a transgender male. The template ensured documentation of defined symptoms and signs of testosterone deficiency; low serum testosterone levels on at least 2 occasions and LH and FSH concentrations; no contraindications to testosterone treatment; discussion of risks and benefits of therapy; and baseline hematocrit (Figure 1). Relevant educational content (eg, risks and benefits of testosterone) was incorporated in the template. The second template was required for the first renewal of testosterone to document adherence to or reason for discontinuation of testosterone; improvement of symptoms and signs; and confirm monitoring hematocrit and testosterone levels during treatment.

Prior to implementation, the PADR template was introduced to HCPs at 2 chief-of-medicine rounds on the diagnosis and evaluation of hypogonadism by a pharmacist and endocrinologist. These educational sessions used case examples and discussions to teach the appropriate use of testosterone therapy in men with hypogonadism. The target audience was PCPs, residents, and other specialists who might prescribe testosterone.

Retrospective Chart Review

To assess the impact of the new testosterone order template on adherence to OIG recommendations, a retrospective chart review was completed comparing the appropriateness of initiating testosterone replacement therapy pretemplate period (July 1 to December 31, 2018) vs posttemplate period (July 1 to December 31, 2019). Inclusion and exclusion criteria were modeled after the 2018 OIG report to allow for comparison with the OIG study population. Eligible veterans in each time period included males who received a new testosterone prescription without having been prescribed testosterone in the previous 12 months. Exclusion criteria included community care network prescriptions (CCNRx); current testosterone prescription from a different VA site; clinic administration of testosterone in the previous 12 months; an organic hypogonadism (ie, Klinefelter syndrome) or gender dysphoria diagnosis; and whether the testosterone prescription was never dispensed (PADR was denied or veteran never had the prescription filled). Veterans who met the inclusion criteria in CPRS were identified by an algorithm developed by the VAPSHCS pharmacoeconomist.

Determining the appropriateness of testosterone prescribing, such as symptoms and laboratory measurements to confirm the diagnosis of hypogonadism, was based on the OIG report and Endocrine Society guidelines. A chart review of the 12 months before testosterone prescribing was completed for each veteran, assessing for documentation of symptoms of testosterone deficiency and laboratory measurements of serum testosterone, LH, and FSH. Also, documentation of a discussion of risks and benefits of testosterone therapy in the 3 months before prescribing was assessed, which matched the timeframe in the VA OIG report.

Interim Analysis

After initial template implementation, the multidisciplinary workgroup reconvened for a preplanned interim analysis in November 2019. The evaluation at this meeting revealed multiple order pathways in CPRS that were not linked to the PADR testosterone order template. Testosterone could be ordered in the generic order dialog, medications by drug class, and medications by alphabet, and endocrinology specialty menus without prompting to complete the testosterone order template or redirection to the restricted drug menu (Figure 2). These alternative testosterone ordering pathways were removed in early December 2019 and additional data collection was conducted for 3 months after discontinuation of alternative order pathways, the posttemplate/no alternative ordering pathways period, from December 7, 2019 to February 29, 2020.

Exclusion of Previous Testosterone Prescriptions Predating Chart Review Period, Subgroup Analysis

In the OIG report and the initial retrospective chart review, only veterans without a testosterone prescription in the previous 12 months were evaluated. To assess whether a previous testosterone prescription influenced completion of the PADR and order template, a further subgroup analysis was conducted that excluded veterans who had a previous testosterone prescription at any time before the chart review periods. Therefore, “new testosterone prescription” refers to a veteran who never had a history of being on testosterone vs “former testosterone prescription,” meaning a patient could have had a previous testosterone prescription > 1 year prior to a new VA testosterone prescription.

Results

One hundred seventy-five veterans with a new testosterone prescription were identified in the pretemplate period; of these 80 (46%) met eligibility criteria; only 20 eligible veterans (25%) had a completed PADR (Figure 3). Ninety-one veterans with a new testosterone prescription were identified in the posttemplate period of which 41 (46%) veterans were eligible; 18 eligible veterans (44%) had a completed PADR, but only 7 (17%) had a completed testosterone order template.

After excluding veterans who had alternative ordering pathways for testosterone, 46 veterans were identified in the posttemplate/no alternative ordering pathways period of which 19 (41%) veterans were eligible. Compared with the posttemplate period, a higher proportion of eligible veterans, 68% (13) had a completed PADR, and 58% (11) had a testosterone order template during the posttemplate/no alternative ordering pathways period.

Discussion

The 2018 OIG report found that VA practitioners demonstrated poor adherence to evidence-based clinical practice guidelines for testosterone treatment in men with hypogonadism. Based on OIG recommendations, we developed a PADR testosterone ordering template to help HCPs improve practice by better adherence to guidelines for the diagnosis and treatment of hypogonadism in veterans. Before implementation of the PADR template, the percentage of veterans at VAPSHCS who had biochemical confirmation of hypogonadism was higher than that in the OIG report. Activation of the PADR testosterone ordering template (with or without removal of options for alternative ordering pathways of testosterone) resulted only in an improvement of laboratory confirmation and evaluation of etiology of hypogonadism. This is when we reasoned that clinicians may have access to prior records and laboratory testing beyond just the past year, and this information may have influenced their use of the PADR template. Subsequently, with exclusion of veterans who were previously prescribed testosterone, implementation of the PADR testosterone order template improved documentation of symptoms of testosterone deficiency, discussion of risks and benefits of testosterone therapy, and biochemical diagnosis and evaluation of hypogonadism relative to the period before implementation.

The lack of effects of implementing the testosterone order template on documentation of symptoms of testosterone deficiency and discussion of risks and benefits of testosterone therapy may be due to local expertise resulting in the relatively high adherence to these guideline recommendations at VAPSHCS before activation of the template vs that in the OIG report. The template improved documentation of the diagnosis and evaluation of hypogonadism for genuinely new testosterone prescriptions in veterans without a history of testosterone prescriptions; while those with a previous prescription had limited improvement. It is possible that in veterans who had testosterone prescribed previously, HCPs may have assumed or had bias that the diagnosis and evaluation of hypogonadism originally made was adequate. This finding underscores the need to develop strategies for reviewing PADR requests where there is historical testosterone use. Perhaps a clinical team member, such as a clinical pharmacist, with the background and training in guidelines for the evaluation of hypogonadism could review PADR requests in veterans with previous testosterone use.

Removal of alternative ordering pathways for testosterone increased the completion rate of PADR requests and the testosterone ordering template, although the latter was not completed in one-third of veterans. Possible reasons for HCPs’ suboptimal completion of the testosterone template despite the PADR initiation include clinicians’ lack of willingness to read the PADR completely and familiarize themselves with the clinical guidelines due to workload demands of PCPs. In addition there maybe pressure from patients to receive testosterone for age-related symptoms due to heavy marketing. In addition, there may have been pharmacists who reviewed the PADR and approved the incomplete testosterone template. At VAPSHCS there were up to 40 pharmacists during different periods reviewing the testosterone PADRs. Likely, not everyone was completely familiar with this implementation process, and a possible future consideration would be further education to staff pharmacists who are verifying these prescriptions. There were several advantages to using this new testosterone order template when HCPs attempted to order a prescription. First, they were prompted to complete the PADR. Subsequently, a pharmacist reviewed the template and approved or rejected the prescription if the template was incomplete. The completed template served as documentation in the electronic health record for the prescribing HCP. The template was constructed to populate the required laboratory tests for ease of use and documentation. In addition, educational information regarding the symptoms and signs of testosterone deficiency, laboratory tests needed to confirm and evaluate hypogonadism, contraindications to testosterone treatment, and risks and benefits of therapy were incorporated into the template to assist HCPs in understanding the requirements for a complete diagnosis and evaluation. Finally, on completion of the template, HCPs were able to order testosterone via link to various testosterone formulations.

Before its implementation, the PADR testosterone order template was introduced to PCPs and internal medicine residents at 2 case-based conferences aimed at the diagnosis and treatment of male hypogonadism. These conferences were well received and helped launch the testosterone PADR template at VAPSHCS. Similar outreach to HCPs who prescribe testosterone is highly recommended in other VA facilities before implementation of the testosterone ordering template. It is possible that more targeted education to other HCPs would have resulted in greater use of the testosterone ordering template and adherence to clinical practice guidelines.

The VAPSHCS multidisciplinary workgroup was essential for the development, implementation, evaluation, and revision of the PADR and testosterone ordering template. The workgroup met routinely to follow up on the ease of installation in CPRS and discuss technical corrections that were needed. This was an essential for quality improvement, as loopholes in CPRS were identified where the HCP could order testosterone without being prompted to use the new PADR testosterone order template (alternative ordering pathways). The workgroup swiftly informed the IT specialist and HPS team to remove alternative ordering pathways of testosterone. Continuous quality improvement evaluations are highly recommended during implementation of the template in other facilities to accommodate specific local modifications that might be needed.

Conclusions

The creation and implementation of a PADR testosterone order template may be a beneficial approach to improve the diagnosis of hypogonadism and facilitate appropriate use of testosterone therapy in veterans in accordance with established clinical practice guidelines, particularly in veterans without any prior testosterone use. Key future strategies to improve testosterone prescribing should focus on identifying clinical team members, such as a local clinical pharmacist, to review and steward PADR requests to ensure that testosterone is indicated, and treatment is appropriately monitored.

Testosterone treatment is clinically indicated when a patient presents with symptoms and signs and biochemical evidence of testosterone deficiency, ie, male hypogonadism. Laboratory confirmation of hypogonadism requires repeatedly low serum testosterone concentrations; between 8 am and 10 am on ≥ 2 separate occasions, and evaluation should include measurement of gonadotropin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) concentrations. If the diagnosis of hypogonadism is established, it is important to determine whether the etiology is due to a structural or congenital disorder of the hypothalamic-pituitary-testicular (HPT) axis (organic hypogonadism) or a comorbid condition that results in suppressed function of an intact HPT axis and that is potentially reversible or treatable (functional hypogonadism).^1,2 Prior to initiation of treatment, clinicians should discuss potential benefits and risks of testosterone and monitoring during treatment, using a shared decision-making process with the patient.¹

Recent studies have reported an increase in testosterone prescriptions and raised concerns regarding health care provider (HCP) prescribing practices despite current clinical practice guidelines from major societies, such as the Endocrine Society. In the US from 2001 to 2011, testosterone use among men aged ≥ 40 years increased more than 3-fold in all age groups.³ Subsequently in the years from 2013 to 2016, prescription rates declined perhaps due to the cardiovascular and stroke concerns.⁴

In the US Department of Veterans Affairs (VA), new testosterone prescriptions across VA medical centers increased from 20,437 in fiscal year (FY) 2009 to 36,394 in FY 2012. Yet only 3.1% of men who received testosterone therapy had 2 or more low morning total or free testosterone concentrations measured; LH and/or FSH levels assessed; and presence of contraindications to therapy documented. Remarkably, 16.5% of these veterans did not have a testosterone level tested prior to being prescribed testosterone. Among veterans who were prescribed testosterone, 1.4% had a diagnosis of prostate cancer, 7.6% had a diagnosis of obstructive sleep apnea (OSA), and 3.5% had elevated hematocrit at baseline.⁵ These findings raised concerns of whether the diagnosis and etiology of hypogonadism were appropriately established and risks were considered before testosterone treatment was initiated.^5,6

To further understand VA prescribing practices of testosterone therapy, a 2018 VA Office of the Inspector General (OIG) report evaluated the initiation and follow-up of testosterone replacement therapy. The OIG randomly sampled and reviewed 1,091 male patients who filled at least 1 outpatient testosterone prescription from VA in FY 2014 and who did not have a prior testosterone prescription in FY 2013. Patients were followed through September 30, 2015. Within 1 year prior to initiating testosterone, only 1.5% had clinical signs and symptoms of testosterone deficiency documented prior to testosterone testing (76% within 18 months of starting testosterone); only 9.1% of veterans had the recommended measurements of 2 low morning testosterone levels; and only 12% had LH and FSH levels measured. Within 3 to 6 months after starting testosterone therapy, only 24% of veterans were assessed for symptom improvement, and 29% to 33% were evaluated for adverse effects, hematocrit levels and adherence to the therapy. The OIG report concluded that VA HCPs were not adhering to guidelines (referencing the Endocrine Society guidelines) when evaluating and treating veterans with testosterone deficiency.⁷

Considering the OIG recommendations and need to improve current practices among providers, VA Puget Sound Health Care System (VAPSHCS) in Washington established a multidisciplinary workgroup consisting of an endocrinologist, geriatrician, primary care provider (PCP), pharmacists, VA information technology (IT) specialist, and health products support (HPS) clinical team in the spring of 2019 to assess and improve testosterone prescribing practices.

Methods

A testosterone order template was developed, approved by VAPSHCS Pharmacy and Therapeutics Committee, and implemented on July 1, 2019, at VAPSHCS, a 1a medical facility caring for more than 112,000 veterans. Given its potential risks and the propensity for varied prescribing practices, testosterone was designated as a restricted drug requiring a prior authorization drug request (PADR) and required completion of the testosterone order template in the Computerized Patient Record System (CPRS).

Testosterone Order Template

The testosterone order template had 2 components. Completion of the template for new testosterone orders was required to initiate treatment unless the patient had known organic hypogonadism or was a transgender male. The template ensured documentation of defined symptoms and signs of testosterone deficiency; low serum testosterone levels on at least 2 occasions and LH and FSH concentrations; no contraindications to testosterone treatment; discussion of risks and benefits of therapy; and baseline hematocrit (Figure 1). Relevant educational content (eg, risks and benefits of testosterone) was incorporated in the template. The second template was required for the first renewal of testosterone to document adherence to or reason for discontinuation of testosterone; improvement of symptoms and signs; and confirm monitoring hematocrit and testosterone levels during treatment.

Prior to implementation, the PADR template was introduced to HCPs at 2 chief-of-medicine rounds on the diagnosis and evaluation of hypogonadism by a pharmacist and endocrinologist. These educational sessions used case examples and discussions to teach the appropriate use of testosterone therapy in men with hypogonadism. The target audience was PCPs, residents, and other specialists who might prescribe testosterone.

Retrospective Chart Review

To assess the impact of the new testosterone order template on adherence to OIG recommendations, a retrospective chart review was completed comparing the appropriateness of initiating testosterone replacement therapy pretemplate period (July 1 to December 31, 2018) vs posttemplate period (July 1 to December 31, 2019). Inclusion and exclusion criteria were modeled after the 2018 OIG report to allow for comparison with the OIG study population. Eligible veterans in each time period included males who received a new testosterone prescription without having been prescribed testosterone in the previous 12 months. Exclusion criteria included community care network prescriptions (CCNRx); current testosterone prescription from a different VA site; clinic administration of testosterone in the previous 12 months; an organic hypogonadism (ie, Klinefelter syndrome) or gender dysphoria diagnosis; and whether the testosterone prescription was never dispensed (PADR was denied or veteran never had the prescription filled). Veterans who met the inclusion criteria in CPRS were identified by an algorithm developed by the VAPSHCS pharmacoeconomist.

Determining the appropriateness of testosterone prescribing, such as symptoms and laboratory measurements to confirm the diagnosis of hypogonadism, was based on the OIG report and Endocrine Society guidelines. A chart review of the 12 months before testosterone prescribing was completed for each veteran, assessing for documentation of symptoms of testosterone deficiency and laboratory measurements of serum testosterone, LH, and FSH. Also, documentation of a discussion of risks and benefits of testosterone therapy in the 3 months before prescribing was assessed, which matched the timeframe in the VA OIG report.

Interim Analysis

After initial template implementation, the multidisciplinary workgroup reconvened for a preplanned interim analysis in November 2019. The evaluation at this meeting revealed multiple order pathways in CPRS that were not linked to the PADR testosterone order template. Testosterone could be ordered in the generic order dialog, medications by drug class, and medications by alphabet, and endocrinology specialty menus without prompting to complete the testosterone order template or redirection to the restricted drug menu (Figure 2). These alternative testosterone ordering pathways were removed in early December 2019 and additional data collection was conducted for 3 months after discontinuation of alternative order pathways, the posttemplate/no alternative ordering pathways period, from December 7, 2019 to February 29, 2020.

Exclusion of Previous Testosterone Prescriptions Predating Chart Review Period, Subgroup Analysis

In the OIG report and the initial retrospective chart review, only veterans without a testosterone prescription in the previous 12 months were evaluated. To assess whether a previous testosterone prescription influenced completion of the PADR and order template, a further subgroup analysis was conducted that excluded veterans who had a previous testosterone prescription at any time before the chart review periods. Therefore, “new testosterone prescription” refers to a veteran who never had a history of being on testosterone vs “former testosterone prescription,” meaning a patient could have had a previous testosterone prescription > 1 year prior to a new VA testosterone prescription.

Results

One hundred seventy-five veterans with a new testosterone prescription were identified in the pretemplate period; of these 80 (46%) met eligibility criteria; only 20 eligible veterans (25%) had a completed PADR (Figure 3). Ninety-one veterans with a new testosterone prescription were identified in the posttemplate period of which 41 (46%) veterans were eligible; 18 eligible veterans (44%) had a completed PADR, but only 7 (17%) had a completed testosterone order template.

After excluding veterans who had alternative ordering pathways for testosterone, 46 veterans were identified in the posttemplate/no alternative ordering pathways period of which 19 (41%) veterans were eligible. Compared with the posttemplate period, a higher proportion of eligible veterans, 68% (13) had a completed PADR, and 58% (11) had a testosterone order template during the posttemplate/no alternative ordering pathways period.

Discussion

The 2018 OIG report found that VA practitioners demonstrated poor adherence to evidence-based clinical practice guidelines for testosterone treatment in men with hypogonadism. Based on OIG recommendations, we developed a PADR testosterone ordering template to help HCPs improve practice by better adherence to guidelines for the diagnosis and treatment of hypogonadism in veterans. Before implementation of the PADR template, the percentage of veterans at VAPSHCS who had biochemical confirmation of hypogonadism was higher than that in the OIG report. Activation of the PADR testosterone ordering template (with or without removal of options for alternative ordering pathways of testosterone) resulted only in an improvement of laboratory confirmation and evaluation of etiology of hypogonadism. This is when we reasoned that clinicians may have access to prior records and laboratory testing beyond just the past year, and this information may have influenced their use of the PADR template. Subsequently, with exclusion of veterans who were previously prescribed testosterone, implementation of the PADR testosterone order template improved documentation of symptoms of testosterone deficiency, discussion of risks and benefits of testosterone therapy, and biochemical diagnosis and evaluation of hypogonadism relative to the period before implementation.

The lack of effects of implementing the testosterone order template on documentation of symptoms of testosterone deficiency and discussion of risks and benefits of testosterone therapy may be due to local expertise resulting in the relatively high adherence to these guideline recommendations at VAPSHCS before activation of the template vs that in the OIG report. The template improved documentation of the diagnosis and evaluation of hypogonadism for genuinely new testosterone prescriptions in veterans without a history of testosterone prescriptions; while those with a previous prescription had limited improvement. It is possible that in veterans who had testosterone prescribed previously, HCPs may have assumed or had bias that the diagnosis and evaluation of hypogonadism originally made was adequate. This finding underscores the need to develop strategies for reviewing PADR requests where there is historical testosterone use. Perhaps a clinical team member, such as a clinical pharmacist, with the background and training in guidelines for the evaluation of hypogonadism could review PADR requests in veterans with previous testosterone use.

Removal of alternative ordering pathways for testosterone increased the completion rate of PADR requests and the testosterone ordering template, although the latter was not completed in one-third of veterans. Possible reasons for HCPs’ suboptimal completion of the testosterone template despite the PADR initiation include clinicians’ lack of willingness to read the PADR completely and familiarize themselves with the clinical guidelines due to workload demands of PCPs. In addition there maybe pressure from patients to receive testosterone for age-related symptoms due to heavy marketing. In addition, there may have been pharmacists who reviewed the PADR and approved the incomplete testosterone template. At VAPSHCS there were up to 40 pharmacists during different periods reviewing the testosterone PADRs. Likely, not everyone was completely familiar with this implementation process, and a possible future consideration would be further education to staff pharmacists who are verifying these prescriptions. There were several advantages to using this new testosterone order template when HCPs attempted to order a prescription. First, they were prompted to complete the PADR. Subsequently, a pharmacist reviewed the template and approved or rejected the prescription if the template was incomplete. The completed template served as documentation in the electronic health record for the prescribing HCP. The template was constructed to populate the required laboratory tests for ease of use and documentation. In addition, educational information regarding the symptoms and signs of testosterone deficiency, laboratory tests needed to confirm and evaluate hypogonadism, contraindications to testosterone treatment, and risks and benefits of therapy were incorporated into the template to assist HCPs in understanding the requirements for a complete diagnosis and evaluation. Finally, on completion of the template, HCPs were able to order testosterone via link to various testosterone formulations.

Before its implementation, the PADR testosterone order template was introduced to PCPs and internal medicine residents at 2 case-based conferences aimed at the diagnosis and treatment of male hypogonadism. These conferences were well received and helped launch the testosterone PADR template at VAPSHCS. Similar outreach to HCPs who prescribe testosterone is highly recommended in other VA facilities before implementation of the testosterone ordering template. It is possible that more targeted education to other HCPs would have resulted in greater use of the testosterone ordering template and adherence to clinical practice guidelines.

The VAPSHCS multidisciplinary workgroup was essential for the development, implementation, evaluation, and revision of the PADR and testosterone ordering template. The workgroup met routinely to follow up on the ease of installation in CPRS and discuss technical corrections that were needed. This was an essential for quality improvement, as loopholes in CPRS were identified where the HCP could order testosterone without being prompted to use the new PADR testosterone order template (alternative ordering pathways). The workgroup swiftly informed the IT specialist and HPS team to remove alternative ordering pathways of testosterone. Continuous quality improvement evaluations are highly recommended during implementation of the template in other facilities to accommodate specific local modifications that might be needed.

Conclusions

The creation and implementation of a PADR testosterone order template may be a beneficial approach to improve the diagnosis of hypogonadism and facilitate appropriate use of testosterone therapy in veterans in accordance with established clinical practice guidelines, particularly in veterans without any prior testosterone use. Key future strategies to improve testosterone prescribing should focus on identifying clinical team members, such as a local clinical pharmacist, to review and steward PADR requests to ensure that testosterone is indicated, and treatment is appropriately monitored.

Testosterone treatment is clinically indicated when a patient presents with symptoms and signs and biochemical evidence of testosterone deficiency, ie, male hypogonadism. Laboratory confirmation of hypogonadism requires repeatedly low serum testosterone concentrations; between 8 am and 10 am on ≥ 2 separate occasions, and evaluation should include measurement of gonadotropin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) concentrations. If the diagnosis of hypogonadism is established, it is important to determine whether the etiology is due to a structural or congenital disorder of the hypothalamic-pituitary-testicular (HPT) axis (organic hypogonadism) or a comorbid condition that results in suppressed function of an intact HPT axis and that is potentially reversible or treatable (functional hypogonadism).^1,2 Prior to initiation of treatment, clinicians should discuss potential benefits and risks of testosterone and monitoring during treatment, using a shared decision-making process with the patient.¹

Recent studies have reported an increase in testosterone prescriptions and raised concerns regarding health care provider (HCP) prescribing practices despite current clinical practice guidelines from major societies, such as the Endocrine Society. In the US from 2001 to 2011, testosterone use among men aged ≥ 40 years increased more than 3-fold in all age groups.³ Subsequently in the years from 2013 to 2016, prescription rates declined perhaps due to the cardiovascular and stroke concerns.⁴

In the US Department of Veterans Affairs (VA), new testosterone prescriptions across VA medical centers increased from 20,437 in fiscal year (FY) 2009 to 36,394 in FY 2012. Yet only 3.1% of men who received testosterone therapy had 2 or more low morning total or free testosterone concentrations measured; LH and/or FSH levels assessed; and presence of contraindications to therapy documented. Remarkably, 16.5% of these veterans did not have a testosterone level tested prior to being prescribed testosterone. Among veterans who were prescribed testosterone, 1.4% had a diagnosis of prostate cancer, 7.6% had a diagnosis of obstructive sleep apnea (OSA), and 3.5% had elevated hematocrit at baseline.⁵ These findings raised concerns of whether the diagnosis and etiology of hypogonadism were appropriately established and risks were considered before testosterone treatment was initiated.^5,6

To further understand VA prescribing practices of testosterone therapy, a 2018 VA Office of the Inspector General (OIG) report evaluated the initiation and follow-up of testosterone replacement therapy. The OIG randomly sampled and reviewed 1,091 male patients who filled at least 1 outpatient testosterone prescription from VA in FY 2014 and who did not have a prior testosterone prescription in FY 2013. Patients were followed through September 30, 2015. Within 1 year prior to initiating testosterone, only 1.5% had clinical signs and symptoms of testosterone deficiency documented prior to testosterone testing (76% within 18 months of starting testosterone); only 9.1% of veterans had the recommended measurements of 2 low morning testosterone levels; and only 12% had LH and FSH levels measured. Within 3 to 6 months after starting testosterone therapy, only 24% of veterans were assessed for symptom improvement, and 29% to 33% were evaluated for adverse effects, hematocrit levels and adherence to the therapy. The OIG report concluded that VA HCPs were not adhering to guidelines (referencing the Endocrine Society guidelines) when evaluating and treating veterans with testosterone deficiency.⁷

Considering the OIG recommendations and need to improve current practices among providers, VA Puget Sound Health Care System (VAPSHCS) in Washington established a multidisciplinary workgroup consisting of an endocrinologist, geriatrician, primary care provider (PCP), pharmacists, VA information technology (IT) specialist, and health products support (HPS) clinical team in the spring of 2019 to assess and improve testosterone prescribing practices.

Methods

A testosterone order template was developed, approved by VAPSHCS Pharmacy and Therapeutics Committee, and implemented on July 1, 2019, at VAPSHCS, a 1a medical facility caring for more than 112,000 veterans. Given its potential risks and the propensity for varied prescribing practices, testosterone was designated as a restricted drug requiring a prior authorization drug request (PADR) and required completion of the testosterone order template in the Computerized Patient Record System (CPRS).

Testosterone Order Template

The testosterone order template had 2 components. Completion of the template for new testosterone orders was required to initiate treatment unless the patient had known organic hypogonadism or was a transgender male. The template ensured documentation of defined symptoms and signs of testosterone deficiency; low serum testosterone levels on at least 2 occasions and LH and FSH concentrations; no contraindications to testosterone treatment; discussion of risks and benefits of therapy; and baseline hematocrit (Figure 1). Relevant educational content (eg, risks and benefits of testosterone) was incorporated in the template. The second template was required for the first renewal of testosterone to document adherence to or reason for discontinuation of testosterone; improvement of symptoms and signs; and confirm monitoring hematocrit and testosterone levels during treatment.

Prior to implementation, the PADR template was introduced to HCPs at 2 chief-of-medicine rounds on the diagnosis and evaluation of hypogonadism by a pharmacist and endocrinologist. These educational sessions used case examples and discussions to teach the appropriate use of testosterone therapy in men with hypogonadism. The target audience was PCPs, residents, and other specialists who might prescribe testosterone.

Retrospective Chart Review

To assess the impact of the new testosterone order template on adherence to OIG recommendations, a retrospective chart review was completed comparing the appropriateness of initiating testosterone replacement therapy pretemplate period (July 1 to December 31, 2018) vs posttemplate period (July 1 to December 31, 2019). Inclusion and exclusion criteria were modeled after the 2018 OIG report to allow for comparison with the OIG study population. Eligible veterans in each time period included males who received a new testosterone prescription without having been prescribed testosterone in the previous 12 months. Exclusion criteria included community care network prescriptions (CCNRx); current testosterone prescription from a different VA site; clinic administration of testosterone in the previous 12 months; an organic hypogonadism (ie, Klinefelter syndrome) or gender dysphoria diagnosis; and whether the testosterone prescription was never dispensed (PADR was denied or veteran never had the prescription filled). Veterans who met the inclusion criteria in CPRS were identified by an algorithm developed by the VAPSHCS pharmacoeconomist.

Determining the appropriateness of testosterone prescribing, such as symptoms and laboratory measurements to confirm the diagnosis of hypogonadism, was based on the OIG report and Endocrine Society guidelines. A chart review of the 12 months before testosterone prescribing was completed for each veteran, assessing for documentation of symptoms of testosterone deficiency and laboratory measurements of serum testosterone, LH, and FSH. Also, documentation of a discussion of risks and benefits of testosterone therapy in the 3 months before prescribing was assessed, which matched the timeframe in the VA OIG report.

Interim Analysis

After initial template implementation, the multidisciplinary workgroup reconvened for a preplanned interim analysis in November 2019. The evaluation at this meeting revealed multiple order pathways in CPRS that were not linked to the PADR testosterone order template. Testosterone could be ordered in the generic order dialog, medications by drug class, and medications by alphabet, and endocrinology specialty menus without prompting to complete the testosterone order template or redirection to the restricted drug menu (Figure 2). These alternative testosterone ordering pathways were removed in early December 2019 and additional data collection was conducted for 3 months after discontinuation of alternative order pathways, the posttemplate/no alternative ordering pathways period, from December 7, 2019 to February 29, 2020.

Exclusion of Previous Testosterone Prescriptions Predating Chart Review Period, Subgroup Analysis

In the OIG report and the initial retrospective chart review, only veterans without a testosterone prescription in the previous 12 months were evaluated. To assess whether a previous testosterone prescription influenced completion of the PADR and order template, a further subgroup analysis was conducted that excluded veterans who had a previous testosterone prescription at any time before the chart review periods. Therefore, “new testosterone prescription” refers to a veteran who never had a history of being on testosterone vs “former testosterone prescription,” meaning a patient could have had a previous testosterone prescription > 1 year prior to a new VA testosterone prescription.

Results

One hundred seventy-five veterans with a new testosterone prescription were identified in the pretemplate period; of these 80 (46%) met eligibility criteria; only 20 eligible veterans (25%) had a completed PADR (Figure 3). Ninety-one veterans with a new testosterone prescription were identified in the posttemplate period of which 41 (46%) veterans were eligible; 18 eligible veterans (44%) had a completed PADR, but only 7 (17%) had a completed testosterone order template.

After excluding veterans who had alternative ordering pathways for testosterone, 46 veterans were identified in the posttemplate/no alternative ordering pathways period of which 19 (41%) veterans were eligible. Compared with the posttemplate period, a higher proportion of eligible veterans, 68% (13) had a completed PADR, and 58% (11) had a testosterone order template during the posttemplate/no alternative ordering pathways period.

Discussion

The 2018 OIG report found that VA practitioners demonstrated poor adherence to evidence-based clinical practice guidelines for testosterone treatment in men with hypogonadism. Based on OIG recommendations, we developed a PADR testosterone ordering template to help HCPs improve practice by better adherence to guidelines for the diagnosis and treatment of hypogonadism in veterans. Before implementation of the PADR template, the percentage of veterans at VAPSHCS who had biochemical confirmation of hypogonadism was higher than that in the OIG report. Activation of the PADR testosterone ordering template (with or without removal of options for alternative ordering pathways of testosterone) resulted only in an improvement of laboratory confirmation and evaluation of etiology of hypogonadism. This is when we reasoned that clinicians may have access to prior records and laboratory testing beyond just the past year, and this information may have influenced their use of the PADR template. Subsequently, with exclusion of veterans who were previously prescribed testosterone, implementation of the PADR testosterone order template improved documentation of symptoms of testosterone deficiency, discussion of risks and benefits of testosterone therapy, and biochemical diagnosis and evaluation of hypogonadism relative to the period before implementation.

The lack of effects of implementing the testosterone order template on documentation of symptoms of testosterone deficiency and discussion of risks and benefits of testosterone therapy may be due to local expertise resulting in the relatively high adherence to these guideline recommendations at VAPSHCS before activation of the template vs that in the OIG report. The template improved documentation of the diagnosis and evaluation of hypogonadism for genuinely new testosterone prescriptions in veterans without a history of testosterone prescriptions; while those with a previous prescription had limited improvement. It is possible that in veterans who had testosterone prescribed previously, HCPs may have assumed or had bias that the diagnosis and evaluation of hypogonadism originally made was adequate. This finding underscores the need to develop strategies for reviewing PADR requests where there is historical testosterone use. Perhaps a clinical team member, such as a clinical pharmacist, with the background and training in guidelines for the evaluation of hypogonadism could review PADR requests in veterans with previous testosterone use.

Removal of alternative ordering pathways for testosterone increased the completion rate of PADR requests and the testosterone ordering template, although the latter was not completed in one-third of veterans. Possible reasons for HCPs’ suboptimal completion of the testosterone template despite the PADR initiation include clinicians’ lack of willingness to read the PADR completely and familiarize themselves with the clinical guidelines due to workload demands of PCPs. In addition there maybe pressure from patients to receive testosterone for age-related symptoms due to heavy marketing. In addition, there may have been pharmacists who reviewed the PADR and approved the incomplete testosterone template. At VAPSHCS there were up to 40 pharmacists during different periods reviewing the testosterone PADRs. Likely, not everyone was completely familiar with this implementation process, and a possible future consideration would be further education to staff pharmacists who are verifying these prescriptions. There were several advantages to using this new testosterone order template when HCPs attempted to order a prescription. First, they were prompted to complete the PADR. Subsequently, a pharmacist reviewed the template and approved or rejected the prescription if the template was incomplete. The completed template served as documentation in the electronic health record for the prescribing HCP. The template was constructed to populate the required laboratory tests for ease of use and documentation. In addition, educational information regarding the symptoms and signs of testosterone deficiency, laboratory tests needed to confirm and evaluate hypogonadism, contraindications to testosterone treatment, and risks and benefits of therapy were incorporated into the template to assist HCPs in understanding the requirements for a complete diagnosis and evaluation. Finally, on completion of the template, HCPs were able to order testosterone via link to various testosterone formulations.

Before its implementation, the PADR testosterone order template was introduced to PCPs and internal medicine residents at 2 case-based conferences aimed at the diagnosis and treatment of male hypogonadism. These conferences were well received and helped launch the testosterone PADR template at VAPSHCS. Similar outreach to HCPs who prescribe testosterone is highly recommended in other VA facilities before implementation of the testosterone ordering template. It is possible that more targeted education to other HCPs would have resulted in greater use of the testosterone ordering template and adherence to clinical practice guidelines.

The VAPSHCS multidisciplinary workgroup was essential for the development, implementation, evaluation, and revision of the PADR and testosterone ordering template. The workgroup met routinely to follow up on the ease of installation in CPRS and discuss technical corrections that were needed. This was an essential for quality improvement, as loopholes in CPRS were identified where the HCP could order testosterone without being prompted to use the new PADR testosterone order template (alternative ordering pathways). The workgroup swiftly informed the IT specialist and HPS team to remove alternative ordering pathways of testosterone. Continuous quality improvement evaluations are highly recommended during implementation of the template in other facilities to accommodate specific local modifications that might be needed.

Conclusions

The creation and implementation of a PADR testosterone order template may be a beneficial approach to improve the diagnosis of hypogonadism and facilitate appropriate use of testosterone therapy in veterans in accordance with established clinical practice guidelines, particularly in veterans without any prior testosterone use. Key future strategies to improve testosterone prescribing should focus on identifying clinical team members, such as a local clinical pharmacist, to review and steward PADR requests to ensure that testosterone is indicated, and treatment is appropriately monitored.

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

A pair of focus groups explored the experience of transgender patients with HIV prevention, finding many were discouraged by experiences of care that was not culturally competent and affirming.

The findings, including other important themes, were published in Pediatrics.

The pair of online asynchronous focus groups, conducted by Holly B. Fontenot, PhD, RN/NP, of the Fenway Institute in Boston, and colleagues, sought input from 30 transgender participants from across the United States. Eleven were aged 13-18 years, and 19 were aged 18-24 years, with an average age of 19. Most (70%) were white, and the remainder were African American (7%), Asian American (3%), multiracial (17%), and other (3%); 10% identified as Hispanic. Participants were given multiple options for reporting gender identity; 27% reported identifying as transgender males, 17% reported identifying as transgender females, and the rest identified with other terms, including 27% using one or more terms.

The quantitative analysis found four common themes, which the study explored in depth: “barriers to self-efficacy in sexual decision making; safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; need for support and education; and desire for affirmative and culturally competent experiences and interactions.”

Based on their findings, the authors suggested ways of improving transgender youth experiences:

• Increasing provider knowledge and skills in providing affirming care through transgender health education programs.
• Addressing the barriers, such as stigma and lack of accessibility.
• Expanding sexual health education to be more inclusive regarding gender identities, sexual orientations, and definitions of sex.

Providers also need to include information on sexually transmitted infection and HIV prevention, including “discussion of safer sexual behaviors, negotiation and consent, sexual and physical assault, condoms, lubrication, STI and HIV testing, human papillomavirus vaccination, and PrEP [preexposure prophylaxis]” the authors emphasized.

Dr. Fontenot and associates determined that this study’s findings were consistent with what’s known about adult transgender patients, but this study provides more context regarding transgender youth experiences.

“It is important to elicit transgender youth experiences and perspectives related to HIV risk and preventive services,” they concluded. “This study provided a greater understanding of barriers to and facilitators of youth obtaining HIV preventive services and sexual health education.”

Limitations of the study included that non–English speaking participants were excluded, and that participants were predominantly white, non-Hispanic, and assigned female sex at birth.

This study was funded by the Centers for Disease Control and Prevention and NORC at The University of Chicago. The authors had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Fontenot HB et al., Pediatrics. 2020. doi: 10.1542/peds.2019-2204.

A pair of focus groups explored the experience of transgender patients with HIV prevention, finding many were discouraged by experiences of care that was not culturally competent and affirming.

The findings, including other important themes, were published in Pediatrics.

The pair of online asynchronous focus groups, conducted by Holly B. Fontenot, PhD, RN/NP, of the Fenway Institute in Boston, and colleagues, sought input from 30 transgender participants from across the United States. Eleven were aged 13-18 years, and 19 were aged 18-24 years, with an average age of 19. Most (70%) were white, and the remainder were African American (7%), Asian American (3%), multiracial (17%), and other (3%); 10% identified as Hispanic. Participants were given multiple options for reporting gender identity; 27% reported identifying as transgender males, 17% reported identifying as transgender females, and the rest identified with other terms, including 27% using one or more terms.

The quantitative analysis found four common themes, which the study explored in depth: “barriers to self-efficacy in sexual decision making; safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; need for support and education; and desire for affirmative and culturally competent experiences and interactions.”

Based on their findings, the authors suggested ways of improving transgender youth experiences:

• Increasing provider knowledge and skills in providing affirming care through transgender health education programs.
• Addressing the barriers, such as stigma and lack of accessibility.
• Expanding sexual health education to be more inclusive regarding gender identities, sexual orientations, and definitions of sex.

Providers also need to include information on sexually transmitted infection and HIV prevention, including “discussion of safer sexual behaviors, negotiation and consent, sexual and physical assault, condoms, lubrication, STI and HIV testing, human papillomavirus vaccination, and PrEP [preexposure prophylaxis]” the authors emphasized.

Dr. Fontenot and associates determined that this study’s findings were consistent with what’s known about adult transgender patients, but this study provides more context regarding transgender youth experiences.

“It is important to elicit transgender youth experiences and perspectives related to HIV risk and preventive services,” they concluded. “This study provided a greater understanding of barriers to and facilitators of youth obtaining HIV preventive services and sexual health education.”

Limitations of the study included that non–English speaking participants were excluded, and that participants were predominantly white, non-Hispanic, and assigned female sex at birth.

This study was funded by the Centers for Disease Control and Prevention and NORC at The University of Chicago. The authors had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Fontenot HB et al., Pediatrics. 2020. doi: 10.1542/peds.2019-2204.

A pair of focus groups explored the experience of transgender patients with HIV prevention, finding many were discouraged by experiences of care that was not culturally competent and affirming.

The findings, including other important themes, were published in Pediatrics.

The pair of online asynchronous focus groups, conducted by Holly B. Fontenot, PhD, RN/NP, of the Fenway Institute in Boston, and colleagues, sought input from 30 transgender participants from across the United States. Eleven were aged 13-18 years, and 19 were aged 18-24 years, with an average age of 19. Most (70%) were white, and the remainder were African American (7%), Asian American (3%), multiracial (17%), and other (3%); 10% identified as Hispanic. Participants were given multiple options for reporting gender identity; 27% reported identifying as transgender males, 17% reported identifying as transgender females, and the rest identified with other terms, including 27% using one or more terms.

The quantitative analysis found four common themes, which the study explored in depth: “barriers to self-efficacy in sexual decision making; safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; need for support and education; and desire for affirmative and culturally competent experiences and interactions.”

Based on their findings, the authors suggested ways of improving transgender youth experiences:

• Increasing provider knowledge and skills in providing affirming care through transgender health education programs.
• Addressing the barriers, such as stigma and lack of accessibility.
• Expanding sexual health education to be more inclusive regarding gender identities, sexual orientations, and definitions of sex.

Providers also need to include information on sexually transmitted infection and HIV prevention, including “discussion of safer sexual behaviors, negotiation and consent, sexual and physical assault, condoms, lubrication, STI and HIV testing, human papillomavirus vaccination, and PrEP [preexposure prophylaxis]” the authors emphasized.

Dr. Fontenot and associates determined that this study’s findings were consistent with what’s known about adult transgender patients, but this study provides more context regarding transgender youth experiences.

“It is important to elicit transgender youth experiences and perspectives related to HIV risk and preventive services,” they concluded. “This study provided a greater understanding of barriers to and facilitators of youth obtaining HIV preventive services and sexual health education.”

Limitations of the study included that non–English speaking participants were excluded, and that participants were predominantly white, non-Hispanic, and assigned female sex at birth.

This study was funded by the Centers for Disease Control and Prevention and NORC at The University of Chicago. The authors had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Fontenot HB et al., Pediatrics. 2020. doi: 10.1542/peds.2019-2204.

Testing rates for HIV in adolescents and young adults with sexually transmitted infections (STIs) are suboptimal, according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.

Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.

Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.

“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.

The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.

Testing rates for HIV in adolescents and young adults with sexually transmitted infections (STIs) are suboptimal, according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.

Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.

Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.

“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.

The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.

Testing rates for HIV in adolescents and young adults with sexually transmitted infections (STIs) are suboptimal, according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.

Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.

Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.

“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.

The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

lfranki@mdedge.com

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

lfranki@mdedge.com

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

lfranki@mdedge.com

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

Pregnant women should be screened for asymptomatic bacteriuria using urine culture because the benefit of reducing pyelonephritis during pregnancy slightly but significantly outweighs the risks of maternal and fetal antibiotic exposure, according to new recommendations set forth by the United States Preventive Services Task Force (USPSTF).

toeytoey2530/Thinkstock

However, the investigating committee reported, there is evidence against screening nonpregnant women and adult men. In fact, the committee found “adequate” evidence of potential harm associated with treating asymptomatic bacteriuria in adults of both sexes, including adverse effects of antibiotics and on the microbiome.

The new document downgrades from A to B the group’s prior recommendation that urine culture screening for asymptomatic bacteriuria should be performed among pregnant women at 12-16 weeks’ gestation or at their first prenatal visit. The USPSTF recommendation to not screen nonpregnant adults retained its D rating, Jerome A. Leis, MD and Christine Soong, MD said in an accompanying editorial.

“Not screening or treating asymptomatic bacteriuria in this population has long been an ironclad recommendation endorsed by the Infectious Diseases Society of America, as well as numerous professional societies as part of the Choosing Wisely campaign,” wrote Dr. Leis of Sunnybrook Health Sciences Centre, Toronto, and Dr. Soong of the University of Toronto. “Restating this steadfast and pervasive recommendation may seem unremarkable and almost pedantic, yet it remains stubbornly disregarded by clinicians across multiple settings.”

The new recommendations were based on a review of 19 studies involving almost 8,500 pregnant and nonpregnant women, as well as a small number of adult men. Most were carried out in the 1960s or 1970s. The most recent ones were published in 2002 and 2015. The dearth of more recent data may have limited some conclusions and certainly highlighted the need for more research, said Jillian T. Henderson, PhD, chair of the committee assigned to investigate the evidence.

“Few studies of asymptomatic bacteriuria screening or treatment in pregnant populations have been conducted in the past 40 years,” wrote Dr. Henderson of Kaiser Permanente Northwest, Portland, and associates. “Historical evidence established asymptomatic bacteriuria screening and treatment as standard obstetric practice in the United States.” But these trials typically were less rigorous than modern studies, and the results are out of touch with modern clinical settings and treatment protocols, the team noted.

Additionally, Dr. Henderson and coauthors said, rates of pyelonephritis were about 10 times higher then than they are now. In the more recent studies, pyelonephritis rates in control groups were 2.2% and 2.5%; in most of the older studies, control group rates ranged from 33% to 36%.

In commissioning the investigation, the task force looked at the following four questions:

Does screening improve health outcomes?

Neither of two studies involving 5,289 women, one from Spain and one from Turkey, addressed this question in nonpregnant women; however, studies that looked at pregnant women generally found that screening did reduce the risk of pyelonephritis by about 70%. The investigators cautioned that these studies were out of date and perhaps methodologically flawed.

The only study that looked at newborn outcomes found no difference in birth weights or premature births between the screened and unscreened cohorts.

No study examined this question in nonpregnant women or men.
 

What are the harms of such screening?

A single study of 372 pregnant women described potential prenatal and perinatal harms associated with screening and treatment. It found a slight increase in congenital abnormalities in the screened cohort (1.6%), compared with those who were not screened (1.1%). However, those who were not screened were presumably not prescribed antibiotics.

Does treatment of screening-detected asymptomatic bacteriuria improve health outcomes?

Twelve trials of pregnant women (2,377) addressed this issue. All but two were conducted in the 1960s and 1970s. Treatment varied widely; sulfonamides were the most common, including the now discarded sulfamethazine and sulfadimethoxine. Dosages and duration of treatment also were considerably higher and longer than current practice.

In all but one study, there were higher rates of pyelonephritis in the control group. A pooled risk analysis indicated that treatment reduced the risk of pyelonephritis by nearly 80% (relative risk, 0.24).

Seven studies found higher rates of low birth weight in infants born to mothers who were treated, but two studies reported a significant reduction in the risk of low birth weight.

Among the six trials that examined perinatal mortality, none found significant associations with treatment.

Five studies examined treatment in nonpregnant women with screening-detected asymptomatic bacteriuria, and one included men as well. Of the four that reported the rate of symptomatic infection or pyelonephritis, none found a significant difference between treatment and control groups. The single study that included men also found no significant difference between treatment and control groups.

Among the three studies that focused on older adults, there also were no significant between-group differences in outcomes.

What harms are associated with treatment of screening-detected asymptomatic bacteriuria?

Seven studies comprised pregnant women. Five reported congenital malformations in the intervention and control groups. Overall, there were very few cases of malformations, with more – although not significantly more – in the control groups.

Evidence related to other infant and maternal harms was “sparsely and inconsistently reported,” Dr. Henderson and coauthors noted, “and there was a lack of evidence on long-term neonatal outcomes after antibiotic treatment of asymptomatic bacteriuria in pregnancy.”

Two studies listed maternal adverse events associated with different treatments including vaginitis and diarrhea with ampicillin and rashes and nausea with nalidixic acid.

In terms of nonpregnant women and men, four studies reported adverse events. None occurred with nitrofurantoin or trimethoprim treatment; however, one study that included daily treatment with ofloxacin noted that 6% withdrew because of adverse events – vertigo and gastrointestinal symptoms.

Treatments didn’t affect hematocrit, bilirubin, serum urea, or nitrogen, although some studies found a slight reduction in serum creatinine.

Although there’s a need for additional research into this question, the new recommendations provide a good reason to further reduce unnecessary antibiotic exposure, Lindsey E. Nicolle, MD, wrote in a second commentary.

These updated recommendations “contribute to the evolution of management of asymptomatic bacteriuria in healthy women,” wrote Dr. Nicolle of the University of Manitoba, Winnipeg. “However, questions remain about the risks and benefits of universal screening for and treatment of asymptomatic bacteriuria in pregnant women in the context of current clinical practice. The effects of changes in fetal-maternal care, of low- compared with high-risk pregnancies, and of health care access need to be understood. In the short term, application of current diagnostic recommendations for identification of persistent symptomatic bacteriuria with a second urine culture may provide an immediate opportunity to limit unnecessary antimicrobial use for some pregnant women.”

No conflicts of interest were reported by the USPSTF authors, nor by Dr. Leis, Dr. Soong, or Dr. Nicolle. The USPSTF report was funded by the Agency for Healthcare Research and Quality.
 

SOURCES: U.S. Preventive Services Task Force. JAMA. 2019;322(12):1188-94; Henderson JT et al. JAMA. 2019;322(12):1195-205; Leis JA and Soong C. JAMA. 2019. doi: 10.1001/jamainternmed.2019.4515; Nicolle LE. JAMA. 2019;322(12):1152-4.

Pregnant women should be screened for asymptomatic bacteriuria using urine culture because the benefit of reducing pyelonephritis during pregnancy slightly but significantly outweighs the risks of maternal and fetal antibiotic exposure, according to new recommendations set forth by the United States Preventive Services Task Force (USPSTF).

toeytoey2530/Thinkstock

However, the investigating committee reported, there is evidence against screening nonpregnant women and adult men. In fact, the committee found “adequate” evidence of potential harm associated with treating asymptomatic bacteriuria in adults of both sexes, including adverse effects of antibiotics and on the microbiome.

The new document downgrades from A to B the group’s prior recommendation that urine culture screening for asymptomatic bacteriuria should be performed among pregnant women at 12-16 weeks’ gestation or at their first prenatal visit. The USPSTF recommendation to not screen nonpregnant adults retained its D rating, Jerome A. Leis, MD and Christine Soong, MD said in an accompanying editorial.

“Not screening or treating asymptomatic bacteriuria in this population has long been an ironclad recommendation endorsed by the Infectious Diseases Society of America, as well as numerous professional societies as part of the Choosing Wisely campaign,” wrote Dr. Leis of Sunnybrook Health Sciences Centre, Toronto, and Dr. Soong of the University of Toronto. “Restating this steadfast and pervasive recommendation may seem unremarkable and almost pedantic, yet it remains stubbornly disregarded by clinicians across multiple settings.”

The new recommendations were based on a review of 19 studies involving almost 8,500 pregnant and nonpregnant women, as well as a small number of adult men. Most were carried out in the 1960s or 1970s. The most recent ones were published in 2002 and 2015. The dearth of more recent data may have limited some conclusions and certainly highlighted the need for more research, said Jillian T. Henderson, PhD, chair of the committee assigned to investigate the evidence.

“Few studies of asymptomatic bacteriuria screening or treatment in pregnant populations have been conducted in the past 40 years,” wrote Dr. Henderson of Kaiser Permanente Northwest, Portland, and associates. “Historical evidence established asymptomatic bacteriuria screening and treatment as standard obstetric practice in the United States.” But these trials typically were less rigorous than modern studies, and the results are out of touch with modern clinical settings and treatment protocols, the team noted.

Additionally, Dr. Henderson and coauthors said, rates of pyelonephritis were about 10 times higher then than they are now. In the more recent studies, pyelonephritis rates in control groups were 2.2% and 2.5%; in most of the older studies, control group rates ranged from 33% to 36%.

In commissioning the investigation, the task force looked at the following four questions:

Does screening improve health outcomes?

Neither of two studies involving 5,289 women, one from Spain and one from Turkey, addressed this question in nonpregnant women; however, studies that looked at pregnant women generally found that screening did reduce the risk of pyelonephritis by about 70%. The investigators cautioned that these studies were out of date and perhaps methodologically flawed.

The only study that looked at newborn outcomes found no difference in birth weights or premature births between the screened and unscreened cohorts.

No study examined this question in nonpregnant women or men.
 

What are the harms of such screening?

A single study of 372 pregnant women described potential prenatal and perinatal harms associated with screening and treatment. It found a slight increase in congenital abnormalities in the screened cohort (1.6%), compared with those who were not screened (1.1%). However, those who were not screened were presumably not prescribed antibiotics.

Does treatment of screening-detected asymptomatic bacteriuria improve health outcomes?

Twelve trials of pregnant women (2,377) addressed this issue. All but two were conducted in the 1960s and 1970s. Treatment varied widely; sulfonamides were the most common, including the now discarded sulfamethazine and sulfadimethoxine. Dosages and duration of treatment also were considerably higher and longer than current practice.

In all but one study, there were higher rates of pyelonephritis in the control group. A pooled risk analysis indicated that treatment reduced the risk of pyelonephritis by nearly 80% (relative risk, 0.24).

Seven studies found higher rates of low birth weight in infants born to mothers who were treated, but two studies reported a significant reduction in the risk of low birth weight.

Among the six trials that examined perinatal mortality, none found significant associations with treatment.

Five studies examined treatment in nonpregnant women with screening-detected asymptomatic bacteriuria, and one included men as well. Of the four that reported the rate of symptomatic infection or pyelonephritis, none found a significant difference between treatment and control groups. The single study that included men also found no significant difference between treatment and control groups.

Among the three studies that focused on older adults, there also were no significant between-group differences in outcomes.

What harms are associated with treatment of screening-detected asymptomatic bacteriuria?

Seven studies comprised pregnant women. Five reported congenital malformations in the intervention and control groups. Overall, there were very few cases of malformations, with more – although not significantly more – in the control groups.

Evidence related to other infant and maternal harms was “sparsely and inconsistently reported,” Dr. Henderson and coauthors noted, “and there was a lack of evidence on long-term neonatal outcomes after antibiotic treatment of asymptomatic bacteriuria in pregnancy.”

Two studies listed maternal adverse events associated with different treatments including vaginitis and diarrhea with ampicillin and rashes and nausea with nalidixic acid.

In terms of nonpregnant women and men, four studies reported adverse events. None occurred with nitrofurantoin or trimethoprim treatment; however, one study that included daily treatment with ofloxacin noted that 6% withdrew because of adverse events – vertigo and gastrointestinal symptoms.

Treatments didn’t affect hematocrit, bilirubin, serum urea, or nitrogen, although some studies found a slight reduction in serum creatinine.

Although there’s a need for additional research into this question, the new recommendations provide a good reason to further reduce unnecessary antibiotic exposure, Lindsey E. Nicolle, MD, wrote in a second commentary.

These updated recommendations “contribute to the evolution of management of asymptomatic bacteriuria in healthy women,” wrote Dr. Nicolle of the University of Manitoba, Winnipeg. “However, questions remain about the risks and benefits of universal screening for and treatment of asymptomatic bacteriuria in pregnant women in the context of current clinical practice. The effects of changes in fetal-maternal care, of low- compared with high-risk pregnancies, and of health care access need to be understood. In the short term, application of current diagnostic recommendations for identification of persistent symptomatic bacteriuria with a second urine culture may provide an immediate opportunity to limit unnecessary antimicrobial use for some pregnant women.”

No conflicts of interest were reported by the USPSTF authors, nor by Dr. Leis, Dr. Soong, or Dr. Nicolle. The USPSTF report was funded by the Agency for Healthcare Research and Quality.
 

SOURCES: U.S. Preventive Services Task Force. JAMA. 2019;322(12):1188-94; Henderson JT et al. JAMA. 2019;322(12):1195-205; Leis JA and Soong C. JAMA. 2019. doi: 10.1001/jamainternmed.2019.4515; Nicolle LE. JAMA. 2019;322(12):1152-4.

Pregnant women should be screened for asymptomatic bacteriuria using urine culture because the benefit of reducing pyelonephritis during pregnancy slightly but significantly outweighs the risks of maternal and fetal antibiotic exposure, according to new recommendations set forth by the United States Preventive Services Task Force (USPSTF).

toeytoey2530/Thinkstock

However, the investigating committee reported, there is evidence against screening nonpregnant women and adult men. In fact, the committee found “adequate” evidence of potential harm associated with treating asymptomatic bacteriuria in adults of both sexes, including adverse effects of antibiotics and on the microbiome.

The new document downgrades from A to B the group’s prior recommendation that urine culture screening for asymptomatic bacteriuria should be performed among pregnant women at 12-16 weeks’ gestation or at their first prenatal visit. The USPSTF recommendation to not screen nonpregnant adults retained its D rating, Jerome A. Leis, MD and Christine Soong, MD said in an accompanying editorial.

“Not screening or treating asymptomatic bacteriuria in this population has long been an ironclad recommendation endorsed by the Infectious Diseases Society of America, as well as numerous professional societies as part of the Choosing Wisely campaign,” wrote Dr. Leis of Sunnybrook Health Sciences Centre, Toronto, and Dr. Soong of the University of Toronto. “Restating this steadfast and pervasive recommendation may seem unremarkable and almost pedantic, yet it remains stubbornly disregarded by clinicians across multiple settings.”

The new recommendations were based on a review of 19 studies involving almost 8,500 pregnant and nonpregnant women, as well as a small number of adult men. Most were carried out in the 1960s or 1970s. The most recent ones were published in 2002 and 2015. The dearth of more recent data may have limited some conclusions and certainly highlighted the need for more research, said Jillian T. Henderson, PhD, chair of the committee assigned to investigate the evidence.

“Few studies of asymptomatic bacteriuria screening or treatment in pregnant populations have been conducted in the past 40 years,” wrote Dr. Henderson of Kaiser Permanente Northwest, Portland, and associates. “Historical evidence established asymptomatic bacteriuria screening and treatment as standard obstetric practice in the United States.” But these trials typically were less rigorous than modern studies, and the results are out of touch with modern clinical settings and treatment protocols, the team noted.

Additionally, Dr. Henderson and coauthors said, rates of pyelonephritis were about 10 times higher then than they are now. In the more recent studies, pyelonephritis rates in control groups were 2.2% and 2.5%; in most of the older studies, control group rates ranged from 33% to 36%.

In commissioning the investigation, the task force looked at the following four questions:

Does screening improve health outcomes?

Neither of two studies involving 5,289 women, one from Spain and one from Turkey, addressed this question in nonpregnant women; however, studies that looked at pregnant women generally found that screening did reduce the risk of pyelonephritis by about 70%. The investigators cautioned that these studies were out of date and perhaps methodologically flawed.

The only study that looked at newborn outcomes found no difference in birth weights or premature births between the screened and unscreened cohorts.

No study examined this question in nonpregnant women or men.
 

What are the harms of such screening?

A single study of 372 pregnant women described potential prenatal and perinatal harms associated with screening and treatment. It found a slight increase in congenital abnormalities in the screened cohort (1.6%), compared with those who were not screened (1.1%). However, those who were not screened were presumably not prescribed antibiotics.

Does treatment of screening-detected asymptomatic bacteriuria improve health outcomes?

Twelve trials of pregnant women (2,377) addressed this issue. All but two were conducted in the 1960s and 1970s. Treatment varied widely; sulfonamides were the most common, including the now discarded sulfamethazine and sulfadimethoxine. Dosages and duration of treatment also were considerably higher and longer than current practice.

In all but one study, there were higher rates of pyelonephritis in the control group. A pooled risk analysis indicated that treatment reduced the risk of pyelonephritis by nearly 80% (relative risk, 0.24).

Seven studies found higher rates of low birth weight in infants born to mothers who were treated, but two studies reported a significant reduction in the risk of low birth weight.

Among the six trials that examined perinatal mortality, none found significant associations with treatment.

Five studies examined treatment in nonpregnant women with screening-detected asymptomatic bacteriuria, and one included men as well. Of the four that reported the rate of symptomatic infection or pyelonephritis, none found a significant difference between treatment and control groups. The single study that included men also found no significant difference between treatment and control groups.

Among the three studies that focused on older adults, there also were no significant between-group differences in outcomes.

What harms are associated with treatment of screening-detected asymptomatic bacteriuria?

Seven studies comprised pregnant women. Five reported congenital malformations in the intervention and control groups. Overall, there were very few cases of malformations, with more – although not significantly more – in the control groups.

Evidence related to other infant and maternal harms was “sparsely and inconsistently reported,” Dr. Henderson and coauthors noted, “and there was a lack of evidence on long-term neonatal outcomes after antibiotic treatment of asymptomatic bacteriuria in pregnancy.”

Two studies listed maternal adverse events associated with different treatments including vaginitis and diarrhea with ampicillin and rashes and nausea with nalidixic acid.

In terms of nonpregnant women and men, four studies reported adverse events. None occurred with nitrofurantoin or trimethoprim treatment; however, one study that included daily treatment with ofloxacin noted that 6% withdrew because of adverse events – vertigo and gastrointestinal symptoms.

Treatments didn’t affect hematocrit, bilirubin, serum urea, or nitrogen, although some studies found a slight reduction in serum creatinine.

Although there’s a need for additional research into this question, the new recommendations provide a good reason to further reduce unnecessary antibiotic exposure, Lindsey E. Nicolle, MD, wrote in a second commentary.

These updated recommendations “contribute to the evolution of management of asymptomatic bacteriuria in healthy women,” wrote Dr. Nicolle of the University of Manitoba, Winnipeg. “However, questions remain about the risks and benefits of universal screening for and treatment of asymptomatic bacteriuria in pregnant women in the context of current clinical practice. The effects of changes in fetal-maternal care, of low- compared with high-risk pregnancies, and of health care access need to be understood. In the short term, application of current diagnostic recommendations for identification of persistent symptomatic bacteriuria with a second urine culture may provide an immediate opportunity to limit unnecessary antimicrobial use for some pregnant women.”

No conflicts of interest were reported by the USPSTF authors, nor by Dr. Leis, Dr. Soong, or Dr. Nicolle. The USPSTF report was funded by the Agency for Healthcare Research and Quality.
 

SOURCES: U.S. Preventive Services Task Force. JAMA. 2019;322(12):1188-94; Henderson JT et al. JAMA. 2019;322(12):1195-205; Leis JA and Soong C. JAMA. 2019. doi: 10.1001/jamainternmed.2019.4515; Nicolle LE. JAMA. 2019;322(12):1152-4.

Catch-up human papillomavirus (HPV) vaccination should be harmonized to include all individuals through 26 years of age, according to a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

This change affects males aged 22 through 26 years; the HPV vaccine is currently recommended for males and females aged 11 or 12 years, with catch-up vaccination through age 21 for males and age 26 for females.

copyright DesignPics/Thinkstock

The change was supported in part by increased interest in simplifying and harmonizing the vaccine schedule, said Lauri Markowitz, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), who presented the HPV work group’s considerations.

In addition, the committee voted 10-4 in favor of catch-up HPV vaccination, based on shared clinical decision making, for all adults aged 27 through 45 years.

Although the current program of HPV vaccination for youth has demonstrated effectiveness, data from multiple models suggest that widespread HPV vaccination for adults older than 26 years is much less cost effective, and would yield relatively small additional health benefits, Dr. Markowitz said.

The HPV work group reviewed data from a range of clinical trials, epidemiology, and natural history, as well as results from five different health economic models. They concluded that an assessment of benefits and harms favors expanding the catch-up vaccination to all individuals through 26 years, said Elissa Meites, MD, of the CDC, who presented the official work group opinion. The group’s opinion on the second question was that the additional population level benefit of expanding HPV vaccination to all adults would be minimal and not a reasonable and effective allocation of resources, but that shared clinical decision making would allow flexibility.

The committee expressed strong opinions about the potential for shared clinical decision making as a policy for vaccination for adults older than 26 years. Some felt that this option was a way to include adults at risk for HPV, such as divorced women with new partners, or women getting married for the first time later in life who might not have been exposed to HPV through other relationships. In addition, supporters noted that the shared clinical decision-making option would allow for potential insurance coverage, and would involve discussion between doctors and patients to assess risk.

However, other committee members felt that any recommendation for older adult vaccination would distract clinicians from the importance and value of HPV vaccination for the target age group of 11- and 12-year-olds, and might divert resources from the younger age group in whom it has shown the most benefit.

Resource allocation was a concern voiced by many committee members. Kelly Moore, MD, MPH, of Vanderbilt University, Nashville, Tenn., said she voted no on expanding vaccination to older adults because “we didn’t have details on shared clinical decision making, in the absence of information on what that meant, and in the presence of supply questions, I didn’t feel comfortable expanding vaccination to a huge population,” she said.

Paul Hunter, MD, of the City of Milwaukee Health Department, also voted no, and expressed concern that expanding the HPV vaccination recommendations to older adults would send the message that vaccination for children and teens is not effective or important.

The text of the new recommendations for routine and catch-up vaccination states that the recommendations “also apply to MSM [men who have sex with men], transgender people, and people with immunocompromising conditions.”

The ACIP members had no financial conflicts to disclose.

Catch-up human papillomavirus (HPV) vaccination should be harmonized to include all individuals through 26 years of age, according to a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

This change affects males aged 22 through 26 years; the HPV vaccine is currently recommended for males and females aged 11 or 12 years, with catch-up vaccination through age 21 for males and age 26 for females.

copyright DesignPics/Thinkstock

The change was supported in part by increased interest in simplifying and harmonizing the vaccine schedule, said Lauri Markowitz, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), who presented the HPV work group’s considerations.

In addition, the committee voted 10-4 in favor of catch-up HPV vaccination, based on shared clinical decision making, for all adults aged 27 through 45 years.

Although the current program of HPV vaccination for youth has demonstrated effectiveness, data from multiple models suggest that widespread HPV vaccination for adults older than 26 years is much less cost effective, and would yield relatively small additional health benefits, Dr. Markowitz said.

The HPV work group reviewed data from a range of clinical trials, epidemiology, and natural history, as well as results from five different health economic models. They concluded that an assessment of benefits and harms favors expanding the catch-up vaccination to all individuals through 26 years, said Elissa Meites, MD, of the CDC, who presented the official work group opinion. The group’s opinion on the second question was that the additional population level benefit of expanding HPV vaccination to all adults would be minimal and not a reasonable and effective allocation of resources, but that shared clinical decision making would allow flexibility.

The committee expressed strong opinions about the potential for shared clinical decision making as a policy for vaccination for adults older than 26 years. Some felt that this option was a way to include adults at risk for HPV, such as divorced women with new partners, or women getting married for the first time later in life who might not have been exposed to HPV through other relationships. In addition, supporters noted that the shared clinical decision-making option would allow for potential insurance coverage, and would involve discussion between doctors and patients to assess risk.

However, other committee members felt that any recommendation for older adult vaccination would distract clinicians from the importance and value of HPV vaccination for the target age group of 11- and 12-year-olds, and might divert resources from the younger age group in whom it has shown the most benefit.

Resource allocation was a concern voiced by many committee members. Kelly Moore, MD, MPH, of Vanderbilt University, Nashville, Tenn., said she voted no on expanding vaccination to older adults because “we didn’t have details on shared clinical decision making, in the absence of information on what that meant, and in the presence of supply questions, I didn’t feel comfortable expanding vaccination to a huge population,” she said.

Paul Hunter, MD, of the City of Milwaukee Health Department, also voted no, and expressed concern that expanding the HPV vaccination recommendations to older adults would send the message that vaccination for children and teens is not effective or important.

The text of the new recommendations for routine and catch-up vaccination states that the recommendations “also apply to MSM [men who have sex with men], transgender people, and people with immunocompromising conditions.”

The ACIP members had no financial conflicts to disclose.

Catch-up human papillomavirus (HPV) vaccination should be harmonized to include all individuals through 26 years of age, according to a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

This change affects males aged 22 through 26 years; the HPV vaccine is currently recommended for males and females aged 11 or 12 years, with catch-up vaccination through age 21 for males and age 26 for females.

copyright DesignPics/Thinkstock

The change was supported in part by increased interest in simplifying and harmonizing the vaccine schedule, said Lauri Markowitz, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), who presented the HPV work group’s considerations.

In addition, the committee voted 10-4 in favor of catch-up HPV vaccination, based on shared clinical decision making, for all adults aged 27 through 45 years.

Although the current program of HPV vaccination for youth has demonstrated effectiveness, data from multiple models suggest that widespread HPV vaccination for adults older than 26 years is much less cost effective, and would yield relatively small additional health benefits, Dr. Markowitz said.

The HPV work group reviewed data from a range of clinical trials, epidemiology, and natural history, as well as results from five different health economic models. They concluded that an assessment of benefits and harms favors expanding the catch-up vaccination to all individuals through 26 years, said Elissa Meites, MD, of the CDC, who presented the official work group opinion. The group’s opinion on the second question was that the additional population level benefit of expanding HPV vaccination to all adults would be minimal and not a reasonable and effective allocation of resources, but that shared clinical decision making would allow flexibility.

The committee expressed strong opinions about the potential for shared clinical decision making as a policy for vaccination for adults older than 26 years. Some felt that this option was a way to include adults at risk for HPV, such as divorced women with new partners, or women getting married for the first time later in life who might not have been exposed to HPV through other relationships. In addition, supporters noted that the shared clinical decision-making option would allow for potential insurance coverage, and would involve discussion between doctors and patients to assess risk.

However, other committee members felt that any recommendation for older adult vaccination would distract clinicians from the importance and value of HPV vaccination for the target age group of 11- and 12-year-olds, and might divert resources from the younger age group in whom it has shown the most benefit.

Resource allocation was a concern voiced by many committee members. Kelly Moore, MD, MPH, of Vanderbilt University, Nashville, Tenn., said she voted no on expanding vaccination to older adults because “we didn’t have details on shared clinical decision making, in the absence of information on what that meant, and in the presence of supply questions, I didn’t feel comfortable expanding vaccination to a huge population,” she said.

Paul Hunter, MD, of the City of Milwaukee Health Department, also voted no, and expressed concern that expanding the HPV vaccination recommendations to older adults would send the message that vaccination for children and teens is not effective or important.

The text of the new recommendations for routine and catch-up vaccination states that the recommendations “also apply to MSM [men who have sex with men], transgender people, and people with immunocompromising conditions.”

The ACIP members had no financial conflicts to disclose.