Dermatology News

A retrospective analysis of Medicare data revealed that between 2000 and 2017, immunohistochemistry (IHC) claims associated with melanoma diagnoses grew from 11% to 51%. Rising utilization — and substantial geographic variation in practice patterns — argue for further research to optimize IHC use in the diagnoses of melanoma, according to the authors.

But with sparse guidance regarding best practices for IHC in melanoma diagnosis, concerns for appropriate use are rising, they wrote in their report, recently published in JAMA Dermatology.

Kenechukwu Ojukwu, MD, MPP, of the department of pathology and laboratory medicine, University of California, Los Angeles, and coinvestigators, searched the Surveillance, Epidemiology, and End Results (SEER)–Medicare database for incident in situ or invasive cutaneous melanoma in patients 65 years and older and accompanying IHC claims made during the month of diagnosis through 14 days afterward.

Among 132,547 melanomas in 116,117 patients, 43,396 (33%) had accompanying IHC claims. Such claims were less common with increasing age, declining from 44% in patients aged 65-74 years to 18% in patients 85 aged years and older. Although melanoma incidence increased throughout the period studied, melanoma mortality rates remained relatively stable.

By summary stage at diagnosis, IHC utilization ranged from 29% of in situ cases to 75% of distant cases. After the researchers controlled for year of diagnosis, IHC use was statistically significantly associated with all demographic, tumor, and geographic characteristics examined, except race and ethnicity. Across all the years of the study, regional usage ranged from a low of 22% in Detroit to a high of 44% in both Louisiana and San Jose-Monterey, California. Figures for 2017 ranged from 39% of cases in Kentucky and Atlanta to 68% in New Mexico.

“Given the extensive use of IHC in clinical practice,” the authors concluded, “studies examining the resulting outcomes of IHC on different domains, such as symptom burden, quality of life, and mortality, are crucial.”

The “notable” regional variation in IHC utilization suggests uncertainty about its optimal employment in clinical practice, and, they wrote, “these findings highlight the need for research to identify where IHC provides the most value and to develop guidelines regarding the appropriate use of IHC.”

In an accompanying JAMA Dermatology editorial, Alexandra Flamm, MD, wrote, “now is an exciting time to practice dermatopathology, with an increased number of ancillary tests, such as IHC, that can be used to diagnose malignant neoplasms more precisely and to more accurately determine prognosis and therapeutic options in this age of precision medicine”.

However, added Dr. Flamm, a dermatologist and dermatopathologist at New York University, New York City, the increasing number of ancillary tests is fueling awareness of appropriate use and the importance of ensuring high-quality, value-based healthcare. “With this increased scrutiny on the appropriateness of ancillary histopathologic testing within dermatopathology,” she wrote, “the need is growing for parameters that can be used to guide when to use IHC testing and other ancillary testing.” And using dermatopathologist-developed tools such as American Society of Dermatopathology guidelines for 11 IHC tests can help ensure that appropriate medical decision-making is taken into account when creating these tools, she added.

IHC Usage Growing

“The paper confirms what I already knew,” said Whitney High, MD, JD, who was not involved with the study and was asked to comment on the results. “Use of IHC in dermatopathology has increased substantially, and probably will continue to increase over time.” The societal burden of IHC costs represents a legitimate concern, said Dr. High, professor of dermatology and pathology and director of dermatopathology at the University of Colorado, Aurora.

“However,” he told this news organization, “the histologic diagnosis of melanoma is sometimes substantially subjective — and all physicians, including pathologists, even though they are not providing care in the physical presence of the patient, are fiduciaries.” If an IHC stain would meaningfully improve a patient’s care, he said, physicians should attempt to provide it, unless strictly disallowed by a payer. Controlling medical-care costs might be better left to professional societies to guide care standards over time, he noted.

Dr. High

A retrospective analysis of Medicare data revealed that between 2000 and 2017, immunohistochemistry (IHC) claims associated with melanoma diagnoses grew from 11% to 51%. Rising utilization — and substantial geographic variation in practice patterns — argue for further research to optimize IHC use in the diagnoses of melanoma, according to the authors.

But with sparse guidance regarding best practices for IHC in melanoma diagnosis, concerns for appropriate use are rising, they wrote in their report, recently published in JAMA Dermatology.

Kenechukwu Ojukwu, MD, MPP, of the department of pathology and laboratory medicine, University of California, Los Angeles, and coinvestigators, searched the Surveillance, Epidemiology, and End Results (SEER)–Medicare database for incident in situ or invasive cutaneous melanoma in patients 65 years and older and accompanying IHC claims made during the month of diagnosis through 14 days afterward.

Among 132,547 melanomas in 116,117 patients, 43,396 (33%) had accompanying IHC claims. Such claims were less common with increasing age, declining from 44% in patients aged 65-74 years to 18% in patients 85 aged years and older. Although melanoma incidence increased throughout the period studied, melanoma mortality rates remained relatively stable.

By summary stage at diagnosis, IHC utilization ranged from 29% of in situ cases to 75% of distant cases. After the researchers controlled for year of diagnosis, IHC use was statistically significantly associated with all demographic, tumor, and geographic characteristics examined, except race and ethnicity. Across all the years of the study, regional usage ranged from a low of 22% in Detroit to a high of 44% in both Louisiana and San Jose-Monterey, California. Figures for 2017 ranged from 39% of cases in Kentucky and Atlanta to 68% in New Mexico.

“Given the extensive use of IHC in clinical practice,” the authors concluded, “studies examining the resulting outcomes of IHC on different domains, such as symptom burden, quality of life, and mortality, are crucial.”

The “notable” regional variation in IHC utilization suggests uncertainty about its optimal employment in clinical practice, and, they wrote, “these findings highlight the need for research to identify where IHC provides the most value and to develop guidelines regarding the appropriate use of IHC.”

In an accompanying JAMA Dermatology editorial, Alexandra Flamm, MD, wrote, “now is an exciting time to practice dermatopathology, with an increased number of ancillary tests, such as IHC, that can be used to diagnose malignant neoplasms more precisely and to more accurately determine prognosis and therapeutic options in this age of precision medicine”.

However, added Dr. Flamm, a dermatologist and dermatopathologist at New York University, New York City, the increasing number of ancillary tests is fueling awareness of appropriate use and the importance of ensuring high-quality, value-based healthcare. “With this increased scrutiny on the appropriateness of ancillary histopathologic testing within dermatopathology,” she wrote, “the need is growing for parameters that can be used to guide when to use IHC testing and other ancillary testing.” And using dermatopathologist-developed tools such as American Society of Dermatopathology guidelines for 11 IHC tests can help ensure that appropriate medical decision-making is taken into account when creating these tools, she added.

IHC Usage Growing

“The paper confirms what I already knew,” said Whitney High, MD, JD, who was not involved with the study and was asked to comment on the results. “Use of IHC in dermatopathology has increased substantially, and probably will continue to increase over time.” The societal burden of IHC costs represents a legitimate concern, said Dr. High, professor of dermatology and pathology and director of dermatopathology at the University of Colorado, Aurora.

“However,” he told this news organization, “the histologic diagnosis of melanoma is sometimes substantially subjective — and all physicians, including pathologists, even though they are not providing care in the physical presence of the patient, are fiduciaries.” If an IHC stain would meaningfully improve a patient’s care, he said, physicians should attempt to provide it, unless strictly disallowed by a payer. Controlling medical-care costs might be better left to professional societies to guide care standards over time, he noted.

Dr. High

A retrospective analysis of Medicare data revealed that between 2000 and 2017, immunohistochemistry (IHC) claims associated with melanoma diagnoses grew from 11% to 51%. Rising utilization — and substantial geographic variation in practice patterns — argue for further research to optimize IHC use in the diagnoses of melanoma, according to the authors.

But with sparse guidance regarding best practices for IHC in melanoma diagnosis, concerns for appropriate use are rising, they wrote in their report, recently published in JAMA Dermatology.

Kenechukwu Ojukwu, MD, MPP, of the department of pathology and laboratory medicine, University of California, Los Angeles, and coinvestigators, searched the Surveillance, Epidemiology, and End Results (SEER)–Medicare database for incident in situ or invasive cutaneous melanoma in patients 65 years and older and accompanying IHC claims made during the month of diagnosis through 14 days afterward.

Among 132,547 melanomas in 116,117 patients, 43,396 (33%) had accompanying IHC claims. Such claims were less common with increasing age, declining from 44% in patients aged 65-74 years to 18% in patients 85 aged years and older. Although melanoma incidence increased throughout the period studied, melanoma mortality rates remained relatively stable.

By summary stage at diagnosis, IHC utilization ranged from 29% of in situ cases to 75% of distant cases. After the researchers controlled for year of diagnosis, IHC use was statistically significantly associated with all demographic, tumor, and geographic characteristics examined, except race and ethnicity. Across all the years of the study, regional usage ranged from a low of 22% in Detroit to a high of 44% in both Louisiana and San Jose-Monterey, California. Figures for 2017 ranged from 39% of cases in Kentucky and Atlanta to 68% in New Mexico.

“Given the extensive use of IHC in clinical practice,” the authors concluded, “studies examining the resulting outcomes of IHC on different domains, such as symptom burden, quality of life, and mortality, are crucial.”

The “notable” regional variation in IHC utilization suggests uncertainty about its optimal employment in clinical practice, and, they wrote, “these findings highlight the need for research to identify where IHC provides the most value and to develop guidelines regarding the appropriate use of IHC.”

In an accompanying JAMA Dermatology editorial, Alexandra Flamm, MD, wrote, “now is an exciting time to practice dermatopathology, with an increased number of ancillary tests, such as IHC, that can be used to diagnose malignant neoplasms more precisely and to more accurately determine prognosis and therapeutic options in this age of precision medicine”.

However, added Dr. Flamm, a dermatologist and dermatopathologist at New York University, New York City, the increasing number of ancillary tests is fueling awareness of appropriate use and the importance of ensuring high-quality, value-based healthcare. “With this increased scrutiny on the appropriateness of ancillary histopathologic testing within dermatopathology,” she wrote, “the need is growing for parameters that can be used to guide when to use IHC testing and other ancillary testing.” And using dermatopathologist-developed tools such as American Society of Dermatopathology guidelines for 11 IHC tests can help ensure that appropriate medical decision-making is taken into account when creating these tools, she added.

IHC Usage Growing

“The paper confirms what I already knew,” said Whitney High, MD, JD, who was not involved with the study and was asked to comment on the results. “Use of IHC in dermatopathology has increased substantially, and probably will continue to increase over time.” The societal burden of IHC costs represents a legitimate concern, said Dr. High, professor of dermatology and pathology and director of dermatopathology at the University of Colorado, Aurora.

“However,” he told this news organization, “the histologic diagnosis of melanoma is sometimes substantially subjective — and all physicians, including pathologists, even though they are not providing care in the physical presence of the patient, are fiduciaries.” If an IHC stain would meaningfully improve a patient’s care, he said, physicians should attempt to provide it, unless strictly disallowed by a payer. Controlling medical-care costs might be better left to professional societies to guide care standards over time, he noted.

Dr. High

Nonprofit hospitals created largely to serve the poor are adding concierge physician practices, charging patients annual membership fees of $2,000 or more for easier access to their doctors.

It’s a trend that began decades ago with physician practices. Thousands of doctors have shifted to the concierge model, in which they can increase their income while decreasing their patient load.

Northwestern Medicine in Chicago, Penn Medicine in Philadelphia, University Hospitals in the Cleveland area, and Baptist Health in Miami are among the large hospital systems offering concierge physician services. The fees, which can exceed $4,000 a year, are in addition to copayments, deductibles, and other charges not paid by patients’ insurance plans.

Critics of concierge medicine say the practice exacerbates primary care shortages, ensuring access only for the affluent, while driving up health care costs. But for tax-exempt hospitals, the financial benefits can be twofold. Concierge fees provide new revenue directly and serve as a tool to help recruit and retain physicians. Those doctors then provide lucrative referrals of their well-heeled patients to the hospitals that employ them.

“Hospitals are attracted to physicians that offer concierge services because their patients do not come with bad debts or a need for charity care, and most of them have private insurance which pays the hospital very well,” said Gerard Anderson, a hospital finance expert at Johns Hopkins University.

“They are the ideal patient, from the hospitals’ perspective.”

Concierge physicians typically limit their practices to a few hundred patients, compared with a couple of thousand for a traditional primary care doctor, so they can promise immediate access and longer visits.

“Every time we see these models expand, we are contracting the availability of primary care doctors for the general population,” said Jewel Mullen, associate dean for health equity at the University of Texas-Austin’s Dell Medical School. The former Connecticut health commissioner said concierge doctors join large hospital systems because of the institutions’ reputations, while hospitals sign up concierge physicians to ensure referrals to specialists and inpatient care. “It helps hospitals secure a bigger piece of their market,” she said.

Concierge physicians typically promise same-day or next-day appointments. Many provide patients their mobile phone number.

Aaron Klein, who oversees the concierge physician practices at Baptist Health, said the program was initially intended to serve donors.

“High-end donors wanted to make sure they have doctors to care for them,” he said.

Baptist opened its concierge program in 2019 and now has three practices across South Florida, where patients pay $2,500 a year.

“My philosophy is: It’s better to give world-class care to a few hundred patients rather than provide inadequate care to a few thousand patients,” Klein said.

Concierge physician practices started more than 20 years ago, mainly in upscale areas such as Boca Raton, Florida, and La Jolla, California. They catered mostly to wealthy retirees willing to pay extra for better physician access. Some of the first physician practices to enter the business were backed by private equity firms.

One of the largest, Boca Raton-based MDVIP, has more than 1,100 physicians and more than 390,000 patients. It was started in 2000, and since 2014 private equity firms have owned a majority stake in the company.

Some concierge physicians say their more attentive care means healthier patients. A study published last year by researchers at the University of California-Berkeley and University of Pennsylvania found no impact on mortality rates. What the study did find: higher costs.

Using Medicare claims data, the researchers found that concierge medicine enrollment corresponded with a 30%-50% increase in total health care spending by patients.

For hospitals, “this is an extension of them consolidating the market,” said Adam Leive, a study co-author and an assistant professor of public policy at UC Berkeley. Inova Health Care Services in Fairfax, Virginia, one of the state’s largest tax-exempt hospital chains, employs 18 concierge doctors, who each handle no more than 400 patients. Those patients pay $2,200 a year for the privilege.

George Salem, 70, of McLean, Virginia, has been a patient in Inova’s concierge practice for several years along with his wife. Earlier this year he slammed his finger in a hotel door, he said. As soon as he got home, he called his physician, who saw him immediately and stitched up the wound. He said he sees his doctor about 10 to 12 times a year.

“I loved my internist before, but it was impossible to get to see him,” Salem said. Immediate access to his doctor “very much gives me peace of mind,” he said.

Craig Cheifetz, a vice president at Inova who oversees the concierge program, said the hospital system took interest in the model after MDVIP began moving aggressively into the Washington, D.C., suburbs about a decade ago. Today, Inova’s program has 6,000 patients.

Cheifetz disputes the charge that concierge physician programs exacerbate primary care shortages. The model keeps doctors who were considering retiring early in the business with a lighter caseload, he said. And the fees amount to no more than a few dollars a day — about what some people spend on coffee, he said.

“Inova has an incredible primary care network for those who can’t afford the concierge care,” he said. “We are still providing all that is necessary in primary care for those who need it.”

Some hospitals are starting concierge physician practices far from their home locations. For example, Tampa General Hospital in Florida last year opened a concierge practice in upper-middle-class Palm Beach Gardens, a roughly three-hour drive from Tampa. Mount Sinai Health System in New York runs a concierge physician practice in West Palm Beach.

NCH Healthcare System in Naples, Florida, employs 12 concierge physicians who treat about 3,000 patients total. “We found a need in this community for those who wanted a more personalized health care experience,” said James Brinkert, regional administrator for the system. Members pay an annual fee of at least $3,500.

NCH patients whose doctors convert to concierge and who don’t want to pay the membership fee are referred to other primary care practices or to urgent care, Brinkert said.

KFF Health News  is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about  KFF .

Nonprofit hospitals created largely to serve the poor are adding concierge physician practices, charging patients annual membership fees of $2,000 or more for easier access to their doctors.

It’s a trend that began decades ago with physician practices. Thousands of doctors have shifted to the concierge model, in which they can increase their income while decreasing their patient load.

Northwestern Medicine in Chicago, Penn Medicine in Philadelphia, University Hospitals in the Cleveland area, and Baptist Health in Miami are among the large hospital systems offering concierge physician services. The fees, which can exceed $4,000 a year, are in addition to copayments, deductibles, and other charges not paid by patients’ insurance plans.

Critics of concierge medicine say the practice exacerbates primary care shortages, ensuring access only for the affluent, while driving up health care costs. But for tax-exempt hospitals, the financial benefits can be twofold. Concierge fees provide new revenue directly and serve as a tool to help recruit and retain physicians. Those doctors then provide lucrative referrals of their well-heeled patients to the hospitals that employ them.

“Hospitals are attracted to physicians that offer concierge services because their patients do not come with bad debts or a need for charity care, and most of them have private insurance which pays the hospital very well,” said Gerard Anderson, a hospital finance expert at Johns Hopkins University.

“They are the ideal patient, from the hospitals’ perspective.”

Concierge physicians typically limit their practices to a few hundred patients, compared with a couple of thousand for a traditional primary care doctor, so they can promise immediate access and longer visits.

“Every time we see these models expand, we are contracting the availability of primary care doctors for the general population,” said Jewel Mullen, associate dean for health equity at the University of Texas-Austin’s Dell Medical School. The former Connecticut health commissioner said concierge doctors join large hospital systems because of the institutions’ reputations, while hospitals sign up concierge physicians to ensure referrals to specialists and inpatient care. “It helps hospitals secure a bigger piece of their market,” she said.

Concierge physicians typically promise same-day or next-day appointments. Many provide patients their mobile phone number.

Aaron Klein, who oversees the concierge physician practices at Baptist Health, said the program was initially intended to serve donors.

“High-end donors wanted to make sure they have doctors to care for them,” he said.

Baptist opened its concierge program in 2019 and now has three practices across South Florida, where patients pay $2,500 a year.

“My philosophy is: It’s better to give world-class care to a few hundred patients rather than provide inadequate care to a few thousand patients,” Klein said.

Concierge physician practices started more than 20 years ago, mainly in upscale areas such as Boca Raton, Florida, and La Jolla, California. They catered mostly to wealthy retirees willing to pay extra for better physician access. Some of the first physician practices to enter the business were backed by private equity firms.

One of the largest, Boca Raton-based MDVIP, has more than 1,100 physicians and more than 390,000 patients. It was started in 2000, and since 2014 private equity firms have owned a majority stake in the company.

Some concierge physicians say their more attentive care means healthier patients. A study published last year by researchers at the University of California-Berkeley and University of Pennsylvania found no impact on mortality rates. What the study did find: higher costs.

Using Medicare claims data, the researchers found that concierge medicine enrollment corresponded with a 30%-50% increase in total health care spending by patients.

For hospitals, “this is an extension of them consolidating the market,” said Adam Leive, a study co-author and an assistant professor of public policy at UC Berkeley. Inova Health Care Services in Fairfax, Virginia, one of the state’s largest tax-exempt hospital chains, employs 18 concierge doctors, who each handle no more than 400 patients. Those patients pay $2,200 a year for the privilege.

George Salem, 70, of McLean, Virginia, has been a patient in Inova’s concierge practice for several years along with his wife. Earlier this year he slammed his finger in a hotel door, he said. As soon as he got home, he called his physician, who saw him immediately and stitched up the wound. He said he sees his doctor about 10 to 12 times a year.

“I loved my internist before, but it was impossible to get to see him,” Salem said. Immediate access to his doctor “very much gives me peace of mind,” he said.

Craig Cheifetz, a vice president at Inova who oversees the concierge program, said the hospital system took interest in the model after MDVIP began moving aggressively into the Washington, D.C., suburbs about a decade ago. Today, Inova’s program has 6,000 patients.

Cheifetz disputes the charge that concierge physician programs exacerbate primary care shortages. The model keeps doctors who were considering retiring early in the business with a lighter caseload, he said. And the fees amount to no more than a few dollars a day — about what some people spend on coffee, he said.

“Inova has an incredible primary care network for those who can’t afford the concierge care,” he said. “We are still providing all that is necessary in primary care for those who need it.”

Some hospitals are starting concierge physician practices far from their home locations. For example, Tampa General Hospital in Florida last year opened a concierge practice in upper-middle-class Palm Beach Gardens, a roughly three-hour drive from Tampa. Mount Sinai Health System in New York runs a concierge physician practice in West Palm Beach.

NCH Healthcare System in Naples, Florida, employs 12 concierge physicians who treat about 3,000 patients total. “We found a need in this community for those who wanted a more personalized health care experience,” said James Brinkert, regional administrator for the system. Members pay an annual fee of at least $3,500.

NCH patients whose doctors convert to concierge and who don’t want to pay the membership fee are referred to other primary care practices or to urgent care, Brinkert said.

KFF Health News  is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about  KFF .

Nonprofit hospitals created largely to serve the poor are adding concierge physician practices, charging patients annual membership fees of $2,000 or more for easier access to their doctors.

It’s a trend that began decades ago with physician practices. Thousands of doctors have shifted to the concierge model, in which they can increase their income while decreasing their patient load.

Northwestern Medicine in Chicago, Penn Medicine in Philadelphia, University Hospitals in the Cleveland area, and Baptist Health in Miami are among the large hospital systems offering concierge physician services. The fees, which can exceed $4,000 a year, are in addition to copayments, deductibles, and other charges not paid by patients’ insurance plans.

Critics of concierge medicine say the practice exacerbates primary care shortages, ensuring access only for the affluent, while driving up health care costs. But for tax-exempt hospitals, the financial benefits can be twofold. Concierge fees provide new revenue directly and serve as a tool to help recruit and retain physicians. Those doctors then provide lucrative referrals of their well-heeled patients to the hospitals that employ them.

“Hospitals are attracted to physicians that offer concierge services because their patients do not come with bad debts or a need for charity care, and most of them have private insurance which pays the hospital very well,” said Gerard Anderson, a hospital finance expert at Johns Hopkins University.

“They are the ideal patient, from the hospitals’ perspective.”

Concierge physicians typically limit their practices to a few hundred patients, compared with a couple of thousand for a traditional primary care doctor, so they can promise immediate access and longer visits.

“Every time we see these models expand, we are contracting the availability of primary care doctors for the general population,” said Jewel Mullen, associate dean for health equity at the University of Texas-Austin’s Dell Medical School. The former Connecticut health commissioner said concierge doctors join large hospital systems because of the institutions’ reputations, while hospitals sign up concierge physicians to ensure referrals to specialists and inpatient care. “It helps hospitals secure a bigger piece of their market,” she said.

Concierge physicians typically promise same-day or next-day appointments. Many provide patients their mobile phone number.

Aaron Klein, who oversees the concierge physician practices at Baptist Health, said the program was initially intended to serve donors.

“High-end donors wanted to make sure they have doctors to care for them,” he said.

Baptist opened its concierge program in 2019 and now has three practices across South Florida, where patients pay $2,500 a year.

“My philosophy is: It’s better to give world-class care to a few hundred patients rather than provide inadequate care to a few thousand patients,” Klein said.

Concierge physician practices started more than 20 years ago, mainly in upscale areas such as Boca Raton, Florida, and La Jolla, California. They catered mostly to wealthy retirees willing to pay extra for better physician access. Some of the first physician practices to enter the business were backed by private equity firms.

One of the largest, Boca Raton-based MDVIP, has more than 1,100 physicians and more than 390,000 patients. It was started in 2000, and since 2014 private equity firms have owned a majority stake in the company.

Some concierge physicians say their more attentive care means healthier patients. A study published last year by researchers at the University of California-Berkeley and University of Pennsylvania found no impact on mortality rates. What the study did find: higher costs.

Using Medicare claims data, the researchers found that concierge medicine enrollment corresponded with a 30%-50% increase in total health care spending by patients.

For hospitals, “this is an extension of them consolidating the market,” said Adam Leive, a study co-author and an assistant professor of public policy at UC Berkeley. Inova Health Care Services in Fairfax, Virginia, one of the state’s largest tax-exempt hospital chains, employs 18 concierge doctors, who each handle no more than 400 patients. Those patients pay $2,200 a year for the privilege.

George Salem, 70, of McLean, Virginia, has been a patient in Inova’s concierge practice for several years along with his wife. Earlier this year he slammed his finger in a hotel door, he said. As soon as he got home, he called his physician, who saw him immediately and stitched up the wound. He said he sees his doctor about 10 to 12 times a year.

“I loved my internist before, but it was impossible to get to see him,” Salem said. Immediate access to his doctor “very much gives me peace of mind,” he said.

Craig Cheifetz, a vice president at Inova who oversees the concierge program, said the hospital system took interest in the model after MDVIP began moving aggressively into the Washington, D.C., suburbs about a decade ago. Today, Inova’s program has 6,000 patients.

Cheifetz disputes the charge that concierge physician programs exacerbate primary care shortages. The model keeps doctors who were considering retiring early in the business with a lighter caseload, he said. And the fees amount to no more than a few dollars a day — about what some people spend on coffee, he said.

“Inova has an incredible primary care network for those who can’t afford the concierge care,” he said. “We are still providing all that is necessary in primary care for those who need it.”

Some hospitals are starting concierge physician practices far from their home locations. For example, Tampa General Hospital in Florida last year opened a concierge practice in upper-middle-class Palm Beach Gardens, a roughly three-hour drive from Tampa. Mount Sinai Health System in New York runs a concierge physician practice in West Palm Beach.

NCH Healthcare System in Naples, Florida, employs 12 concierge physicians who treat about 3,000 patients total. “We found a need in this community for those who wanted a more personalized health care experience,” said James Brinkert, regional administrator for the system. Members pay an annual fee of at least $3,500.

NCH patients whose doctors convert to concierge and who don’t want to pay the membership fee are referred to other primary care practices or to urgent care, Brinkert said.

KFF Health News  is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about  KFF .

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

SAN DIEGO — When Jennifer Adams, MD, recently entered the search term “warts” on the ClinicalTrials.gov web site, nearly 240 results popped up.

“There is a lot of research activity around this topic,” Dr. Adams, vice chair of the department of dermatology at the University of Nebraska Medical Center, said at the annual meeting of the American Academy of Dermatology. “We just don’t have fantastic, well-run trials on many of the currently available treatments.”

In a 2012 Cochrane review on the topical treatment of non-genital cutaneous warts, authors drew from 85 trials involving 8,815 randomized patients. They found that most warts spontaneously resolved, and the authors determined salicylic acid to be safe and modestly beneficial. Specifically, trials of salicylic acid (SA) versus placebo showed that the former significantly increased the chance of clearance of warts at all sites (risk ratio, 1.56, 95% confidence interval [CI], 1.20-2.03). A meta-analysis of cryotherapy versus placebo for warts at all sites favored neither intervention nor control (RR, 1.45, 95% CI, 0.65-3.23).

“The authors determined that there is less evidence for cryotherapy but stated that it may work when salicylic acid does not, or in combination with salicylic acid,” Dr. Adams said. “However, salicylic acid and cryotherapy don’t do enough for our patients [with warts]. There are a lot of situations where we need to reach further into the toolbox.”

A 2021 review article listed many options for managing difficult-to-treat warts, including intralesional Candida antigen, intralesional measles-mumps-rubella (MMR), intralesional HPV vaccine, intralesional vitamin D, intralesional cidofovir, intralesional bleomycin, and intralesional 5-FU injections, and topical vitamin D, topical cidofovir, and topical bleomycin. According to Dr. Adams, clinical data exist for cidofovir and vitamin D but studies evaluated different formulations, doses, sites of administration, and limited randomized controlled trials.

“Intralesional cidofovir is more effective than the topical form, but intralesional cidofovir can be painful and both forms are expensive,” she said. “Topical vitamin D is less likely to cause dyspigmentation compared to other available treatments, so it’s a great option in skin of color, but it has been less effective compared to some of our other topical treatments.”

Newer Options Promising

On the horizon, berdazimer gel was approved in January of 2024 for the treatment of molluscum but results from trials of its use for extragenital warts are encouraging. Another promising option is topical ionic contraviral therapy (ICVT) with digoxin and furosemide combined, which inhibits cellular potassium influx. A phase 2a randomized controlled trial of 80 adults found a statistically significant reduction in the diameter of cutaneous warts among those who received ICVT compared with those who received placebo (P = .002). “It’s cheap and well tolerated,” Dr. Adams added.

Intralesional approaches to treating warts offer another alternative. A 2020 review of 43 articles concluded that intralesional treatments for warts have equal or superior efficacy to first-line salicylic acid or cryotherapy.

Dr. Adams said that she considers intralesional treatments such as vitamin D, MMR vaccine antigen, and Candida antigen for refractory, numerous, or distant site warts. “Injecting the MMR vaccine into the largest wart every 2 weeks has been found to lead to complete clearance in 60%-68% of cases in one study,” she said. “The benefit is that it’s $21 per dose, which is nice, but as with any vaccination, patients can develop flu-like symptoms as side effects.”

Use of the HPV vaccine for treating cutaneous warts remains controversial, she continued, but it seems to work better in younger patients. In one open-label study that evaluated the HPV vaccine for the treatment of multiple recalcitrant warts, with doses administered at 0. 2, and 6 months, the response rate 3 months after the third dose was 55% among those older than age 26, compared with 84% among those ages 9-26 years.

Another option, intralesional cidofovir, has been shown to be especially effective for refractory warts. “It has also been shown to work for warts in immunocompetent and immunocompromised patients,” Dr. Adams said.

In the realm of adjuvant treatments, microneedling has been found to have similar efficacy to needling, Dr. Adams said, but with minimal pain. “When we combine it with topical treatments like 5-FU, it’s even more efficacious,” she said.

One study found that combining microneedling with topical 5-FU had clearance similar to that of intralesional 5-FU or microneedling alone, but involved fewer treatment sessions and less pain in the combination group.

Autoinoculation has been used to stimulate an immune response in patients with warts, leading to clearance rates of 4% (mild clearance) to 66% (complete clearance) in one study. “We would expect this to work better in immunocompetent patients, but it’s something to keep in mind if you’re limited in the medications you can get for a patient,” Dr. Adams said. Also, results from a systematic review and meta-analysis suggest that systemic retinoids combined with intralesional immunotherapy leads to higher clearance rates and lower rates of recurrence of warts. The top performer among those tested was acitretin plus Candida antigen.

Dr. Adams advised dermatologists who try alternatives to salicylic acid and cryotherapy for warts to be “wary of a lack of high-level evidence” for their use. “They can be helpful for patients who have failed traditional therapies or have a contraindication to the usual go-tos.”

She reported having no relevant financial disclosures.

SAN DIEGO — When Jennifer Adams, MD, recently entered the search term “warts” on the ClinicalTrials.gov web site, nearly 240 results popped up.

“There is a lot of research activity around this topic,” Dr. Adams, vice chair of the department of dermatology at the University of Nebraska Medical Center, said at the annual meeting of the American Academy of Dermatology. “We just don’t have fantastic, well-run trials on many of the currently available treatments.”

In a 2012 Cochrane review on the topical treatment of non-genital cutaneous warts, authors drew from 85 trials involving 8,815 randomized patients. They found that most warts spontaneously resolved, and the authors determined salicylic acid to be safe and modestly beneficial. Specifically, trials of salicylic acid (SA) versus placebo showed that the former significantly increased the chance of clearance of warts at all sites (risk ratio, 1.56, 95% confidence interval [CI], 1.20-2.03). A meta-analysis of cryotherapy versus placebo for warts at all sites favored neither intervention nor control (RR, 1.45, 95% CI, 0.65-3.23).

“The authors determined that there is less evidence for cryotherapy but stated that it may work when salicylic acid does not, or in combination with salicylic acid,” Dr. Adams said. “However, salicylic acid and cryotherapy don’t do enough for our patients [with warts]. There are a lot of situations where we need to reach further into the toolbox.”

A 2021 review article listed many options for managing difficult-to-treat warts, including intralesional Candida antigen, intralesional measles-mumps-rubella (MMR), intralesional HPV vaccine, intralesional vitamin D, intralesional cidofovir, intralesional bleomycin, and intralesional 5-FU injections, and topical vitamin D, topical cidofovir, and topical bleomycin. According to Dr. Adams, clinical data exist for cidofovir and vitamin D but studies evaluated different formulations, doses, sites of administration, and limited randomized controlled trials.

“Intralesional cidofovir is more effective than the topical form, but intralesional cidofovir can be painful and both forms are expensive,” she said. “Topical vitamin D is less likely to cause dyspigmentation compared to other available treatments, so it’s a great option in skin of color, but it has been less effective compared to some of our other topical treatments.”

Newer Options Promising

On the horizon, berdazimer gel was approved in January of 2024 for the treatment of molluscum but results from trials of its use for extragenital warts are encouraging. Another promising option is topical ionic contraviral therapy (ICVT) with digoxin and furosemide combined, which inhibits cellular potassium influx. A phase 2a randomized controlled trial of 80 adults found a statistically significant reduction in the diameter of cutaneous warts among those who received ICVT compared with those who received placebo (P = .002). “It’s cheap and well tolerated,” Dr. Adams added.

Intralesional approaches to treating warts offer another alternative. A 2020 review of 43 articles concluded that intralesional treatments for warts have equal or superior efficacy to first-line salicylic acid or cryotherapy.

Dr. Adams said that she considers intralesional treatments such as vitamin D, MMR vaccine antigen, and Candida antigen for refractory, numerous, or distant site warts. “Injecting the MMR vaccine into the largest wart every 2 weeks has been found to lead to complete clearance in 60%-68% of cases in one study,” she said. “The benefit is that it’s $21 per dose, which is nice, but as with any vaccination, patients can develop flu-like symptoms as side effects.”

Use of the HPV vaccine for treating cutaneous warts remains controversial, she continued, but it seems to work better in younger patients. In one open-label study that evaluated the HPV vaccine for the treatment of multiple recalcitrant warts, with doses administered at 0. 2, and 6 months, the response rate 3 months after the third dose was 55% among those older than age 26, compared with 84% among those ages 9-26 years.

Another option, intralesional cidofovir, has been shown to be especially effective for refractory warts. “It has also been shown to work for warts in immunocompetent and immunocompromised patients,” Dr. Adams said.

In the realm of adjuvant treatments, microneedling has been found to have similar efficacy to needling, Dr. Adams said, but with minimal pain. “When we combine it with topical treatments like 5-FU, it’s even more efficacious,” she said.

One study found that combining microneedling with topical 5-FU had clearance similar to that of intralesional 5-FU or microneedling alone, but involved fewer treatment sessions and less pain in the combination group.

Autoinoculation has been used to stimulate an immune response in patients with warts, leading to clearance rates of 4% (mild clearance) to 66% (complete clearance) in one study. “We would expect this to work better in immunocompetent patients, but it’s something to keep in mind if you’re limited in the medications you can get for a patient,” Dr. Adams said. Also, results from a systematic review and meta-analysis suggest that systemic retinoids combined with intralesional immunotherapy leads to higher clearance rates and lower rates of recurrence of warts. The top performer among those tested was acitretin plus Candida antigen.

Dr. Adams advised dermatologists who try alternatives to salicylic acid and cryotherapy for warts to be “wary of a lack of high-level evidence” for their use. “They can be helpful for patients who have failed traditional therapies or have a contraindication to the usual go-tos.”

She reported having no relevant financial disclosures.

SAN DIEGO — When Jennifer Adams, MD, recently entered the search term “warts” on the ClinicalTrials.gov web site, nearly 240 results popped up.

“There is a lot of research activity around this topic,” Dr. Adams, vice chair of the department of dermatology at the University of Nebraska Medical Center, said at the annual meeting of the American Academy of Dermatology. “We just don’t have fantastic, well-run trials on many of the currently available treatments.”

In a 2012 Cochrane review on the topical treatment of non-genital cutaneous warts, authors drew from 85 trials involving 8,815 randomized patients. They found that most warts spontaneously resolved, and the authors determined salicylic acid to be safe and modestly beneficial. Specifically, trials of salicylic acid (SA) versus placebo showed that the former significantly increased the chance of clearance of warts at all sites (risk ratio, 1.56, 95% confidence interval [CI], 1.20-2.03). A meta-analysis of cryotherapy versus placebo for warts at all sites favored neither intervention nor control (RR, 1.45, 95% CI, 0.65-3.23).

“The authors determined that there is less evidence for cryotherapy but stated that it may work when salicylic acid does not, or in combination with salicylic acid,” Dr. Adams said. “However, salicylic acid and cryotherapy don’t do enough for our patients [with warts]. There are a lot of situations where we need to reach further into the toolbox.”

A 2021 review article listed many options for managing difficult-to-treat warts, including intralesional Candida antigen, intralesional measles-mumps-rubella (MMR), intralesional HPV vaccine, intralesional vitamin D, intralesional cidofovir, intralesional bleomycin, and intralesional 5-FU injections, and topical vitamin D, topical cidofovir, and topical bleomycin. According to Dr. Adams, clinical data exist for cidofovir and vitamin D but studies evaluated different formulations, doses, sites of administration, and limited randomized controlled trials.

“Intralesional cidofovir is more effective than the topical form, but intralesional cidofovir can be painful and both forms are expensive,” she said. “Topical vitamin D is less likely to cause dyspigmentation compared to other available treatments, so it’s a great option in skin of color, but it has been less effective compared to some of our other topical treatments.”

Newer Options Promising

On the horizon, berdazimer gel was approved in January of 2024 for the treatment of molluscum but results from trials of its use for extragenital warts are encouraging. Another promising option is topical ionic contraviral therapy (ICVT) with digoxin and furosemide combined, which inhibits cellular potassium influx. A phase 2a randomized controlled trial of 80 adults found a statistically significant reduction in the diameter of cutaneous warts among those who received ICVT compared with those who received placebo (P = .002). “It’s cheap and well tolerated,” Dr. Adams added.

Intralesional approaches to treating warts offer another alternative. A 2020 review of 43 articles concluded that intralesional treatments for warts have equal or superior efficacy to first-line salicylic acid or cryotherapy.

Dr. Adams said that she considers intralesional treatments such as vitamin D, MMR vaccine antigen, and Candida antigen for refractory, numerous, or distant site warts. “Injecting the MMR vaccine into the largest wart every 2 weeks has been found to lead to complete clearance in 60%-68% of cases in one study,” she said. “The benefit is that it’s $21 per dose, which is nice, but as with any vaccination, patients can develop flu-like symptoms as side effects.”

Use of the HPV vaccine for treating cutaneous warts remains controversial, she continued, but it seems to work better in younger patients. In one open-label study that evaluated the HPV vaccine for the treatment of multiple recalcitrant warts, with doses administered at 0. 2, and 6 months, the response rate 3 months after the third dose was 55% among those older than age 26, compared with 84% among those ages 9-26 years.

Another option, intralesional cidofovir, has been shown to be especially effective for refractory warts. “It has also been shown to work for warts in immunocompetent and immunocompromised patients,” Dr. Adams said.

In the realm of adjuvant treatments, microneedling has been found to have similar efficacy to needling, Dr. Adams said, but with minimal pain. “When we combine it with topical treatments like 5-FU, it’s even more efficacious,” she said.

One study found that combining microneedling with topical 5-FU had clearance similar to that of intralesional 5-FU or microneedling alone, but involved fewer treatment sessions and less pain in the combination group.

Autoinoculation has been used to stimulate an immune response in patients with warts, leading to clearance rates of 4% (mild clearance) to 66% (complete clearance) in one study. “We would expect this to work better in immunocompetent patients, but it’s something to keep in mind if you’re limited in the medications you can get for a patient,” Dr. Adams said. Also, results from a systematic review and meta-analysis suggest that systemic retinoids combined with intralesional immunotherapy leads to higher clearance rates and lower rates of recurrence of warts. The top performer among those tested was acitretin plus Candida antigen.

Dr. Adams advised dermatologists who try alternatives to salicylic acid and cryotherapy for warts to be “wary of a lack of high-level evidence” for their use. “They can be helpful for patients who have failed traditional therapies or have a contraindication to the usual go-tos.”

She reported having no relevant financial disclosures.

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

SAN DIEGO — A novel formulation of polidocanol, an injectable synthetic non-ionic detergent that is approved by the US Food and Drug Administration (FDA) for sclerotherapy, may have a role in excess submental fat reduction, results from a phase 2b trial demonstrated.

The solution, also known as 10XB101, “has been demonstrated to cause adipolysis,” Kavita Darji, MD, an American Society for Dermatologic Surgery (ASDS) cosmetic and dermatologic laser surgery fellow at a practice in San Diego, said during a late-breaking session at the annual meeting of the American Academy of Dermatology. “It shows less inflammation and release of cytokines TNF-alpha and MCP-1 by macrophages than deoxycholic acid, which is currently used for submental fat reduction.”

Dr. Darji

In a phase 2b clinical trial conducted at four sites, investigators enrolled 51 patients and assigned them to one of four dose cohorts: 2%, 3%, or 4.5% 10XB101, or vehicle. Each treatment consisted of up to 50 injections at 0.2 mL per injection, and they were administered up to six times 4 weeks apart. Study endpoints included a composite of the Clinician Submental Fat Score (CSFS) and Patient Submental Fat Score (PSFS) on a 0-4–point scale. The researchers graded local skin reactions such as erythema, edema, tenderness on palpation, bruising, pain, and burning/stinging as 0 (none), 1 (mild), 2 (moderate), or 3 (severe). They also obtained lab tests and performed electrocardiograms.

Dr. Darji and colleagues analyzed two populations: the intent to treat (ITT) population, which included all 51 enrolled subjects who received any injection of the test agent, and a completer population of 40 subjects. “These patients had at least four treatments or completed the treatments per protocol, completed the 4 weeks after final treatment assessments, or did not have any significant protocol deviations that would impact the evaluation of efficacy,” she explained.

To compare how 10XB101 performed compared with deoxycholic acid (Kybella), which is approved by the FDA to improve the appearance of moderate to severe submental fat, the researchers drew from pooled findings of Refine 1 and 2, in which adults received up to six treatment sessions with deoxycholic acid or placebo.

The ITT analysis of the 3% and 4.5% 10XB101 dose groups showed about a fourfold increase in a 2-grade or better improvement in the composite endpoint relative to the pooled findings of deoxycholic acid (62% vs. 16%, respectively). In addition, 80% of the completer population achieved a 2-grade improvement in the composite endpoint. “Importantly, 10% to 33% also received a 3-grade improvement, depending on the dose they were assigned to,” Dr. Darji said.

On average, patients in both cohorts achieved a 1-grade improvement after two treatments, and about 50% achieved a 2-grade improvement after four treatments — which is consistent with a more rapid onset when compared with deoxycholic acid, she said.

Both study endpoints were achieved by 31% of patients in the ITT group vs. 33% of completers, respectively, with the 2% dose; 62% vs. 80% with the 3% dose; and 54% vs. 79% for the 4.5% dose. “This is a 2- to 5-times increase in success” when compared with the results of deoxycholic acid in the published pooled analysis, Dr. Darji said. The researchers measured adverse events by spontaneous and elicited reports and by assessments of recorded local skin reactions. They found that 80% of all measured local skin reactions rated as 0 while 98% of all measured local skin reactions rated as a 0 or 1. One myocardial infarction occurred, which was mild and resolved. This case was not related to the study drug, Dr. Darji said in an interview after the meeting. Otherwise, no safety laboratory or ECG signals were noted.

In findings limited to the 3% dose of 10XB101, mild bruising occurred in 8% of patients at postinjection visit 2, 18% of those at postinjection visit 3, 20% of those at postinjection visit 4, and in 20% of those at postinjection visit 5. Reports of mild pain/burning/stinging occurred in 8% of patients at postinjection visit 2 but at no other subsequent visits. Meanwhile, edema occurred in 42% of patients at postinjection visit 2, 45% of those at postinjection visit 3, 50% of those at postinjection visits 4 and 5, and 38% of those at postinjection visit 6.

“Patients resumed normal activity within 1-3 days and had fewer side effects that lasted longer than 30 days,” Dr. Darji concluded, adding that the results “imply a potential opportunity to expand the treatment to other anatomic areas, which is a future direction.”

One of the session moderators, Andrew Blauvelt, MD, MBA, of Oregon Medical Research Center, Portland, noted that the study was not a head-to-head trial of polidocanol vs. deoxycholic acid, so he cautioned against drawing strong conclusions about the comparative data presented.

Asked to comment on the results Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, said that 10XB101 “showed excellent efficacy with much fewer adverse events when compared to what we found in studies with Kybella, the only currently FDA-approved injection for submental fat reduction.”

Dr. Green

In addition, “much less pain after injection was to me the most obvious differentiator between this and Kybella studies. I look forward to seeing if larger studies confirm the efficacy and safety from this phase 2 study, as 10XB101 has potential to be a more effective, and safer option to reduce submental fat,” he added. He was not involved with the study.

Dr. Darji reported having no disclosures. Mitchel P. Goldman, MD, the study’s lead investigator, is a minority investor in 10XBio, which is developing 10XB101. Dr. Blauvelt and Dr. Green disclosed conflicts of interest from many pharmaceutical companies.

SAN DIEGO — A novel formulation of polidocanol, an injectable synthetic non-ionic detergent that is approved by the US Food and Drug Administration (FDA) for sclerotherapy, may have a role in excess submental fat reduction, results from a phase 2b trial demonstrated.

The solution, also known as 10XB101, “has been demonstrated to cause adipolysis,” Kavita Darji, MD, an American Society for Dermatologic Surgery (ASDS) cosmetic and dermatologic laser surgery fellow at a practice in San Diego, said during a late-breaking session at the annual meeting of the American Academy of Dermatology. “It shows less inflammation and release of cytokines TNF-alpha and MCP-1 by macrophages than deoxycholic acid, which is currently used for submental fat reduction.”

Dr. Darji

In a phase 2b clinical trial conducted at four sites, investigators enrolled 51 patients and assigned them to one of four dose cohorts: 2%, 3%, or 4.5% 10XB101, or vehicle. Each treatment consisted of up to 50 injections at 0.2 mL per injection, and they were administered up to six times 4 weeks apart. Study endpoints included a composite of the Clinician Submental Fat Score (CSFS) and Patient Submental Fat Score (PSFS) on a 0-4–point scale. The researchers graded local skin reactions such as erythema, edema, tenderness on palpation, bruising, pain, and burning/stinging as 0 (none), 1 (mild), 2 (moderate), or 3 (severe). They also obtained lab tests and performed electrocardiograms.

Dr. Darji and colleagues analyzed two populations: the intent to treat (ITT) population, which included all 51 enrolled subjects who received any injection of the test agent, and a completer population of 40 subjects. “These patients had at least four treatments or completed the treatments per protocol, completed the 4 weeks after final treatment assessments, or did not have any significant protocol deviations that would impact the evaluation of efficacy,” she explained.

To compare how 10XB101 performed compared with deoxycholic acid (Kybella), which is approved by the FDA to improve the appearance of moderate to severe submental fat, the researchers drew from pooled findings of Refine 1 and 2, in which adults received up to six treatment sessions with deoxycholic acid or placebo.

The ITT analysis of the 3% and 4.5% 10XB101 dose groups showed about a fourfold increase in a 2-grade or better improvement in the composite endpoint relative to the pooled findings of deoxycholic acid (62% vs. 16%, respectively). In addition, 80% of the completer population achieved a 2-grade improvement in the composite endpoint. “Importantly, 10% to 33% also received a 3-grade improvement, depending on the dose they were assigned to,” Dr. Darji said.

On average, patients in both cohorts achieved a 1-grade improvement after two treatments, and about 50% achieved a 2-grade improvement after four treatments — which is consistent with a more rapid onset when compared with deoxycholic acid, she said.

Both study endpoints were achieved by 31% of patients in the ITT group vs. 33% of completers, respectively, with the 2% dose; 62% vs. 80% with the 3% dose; and 54% vs. 79% for the 4.5% dose. “This is a 2- to 5-times increase in success” when compared with the results of deoxycholic acid in the published pooled analysis, Dr. Darji said. The researchers measured adverse events by spontaneous and elicited reports and by assessments of recorded local skin reactions. They found that 80% of all measured local skin reactions rated as 0 while 98% of all measured local skin reactions rated as a 0 or 1. One myocardial infarction occurred, which was mild and resolved. This case was not related to the study drug, Dr. Darji said in an interview after the meeting. Otherwise, no safety laboratory or ECG signals were noted.

In findings limited to the 3% dose of 10XB101, mild bruising occurred in 8% of patients at postinjection visit 2, 18% of those at postinjection visit 3, 20% of those at postinjection visit 4, and in 20% of those at postinjection visit 5. Reports of mild pain/burning/stinging occurred in 8% of patients at postinjection visit 2 but at no other subsequent visits. Meanwhile, edema occurred in 42% of patients at postinjection visit 2, 45% of those at postinjection visit 3, 50% of those at postinjection visits 4 and 5, and 38% of those at postinjection visit 6.

“Patients resumed normal activity within 1-3 days and had fewer side effects that lasted longer than 30 days,” Dr. Darji concluded, adding that the results “imply a potential opportunity to expand the treatment to other anatomic areas, which is a future direction.”

One of the session moderators, Andrew Blauvelt, MD, MBA, of Oregon Medical Research Center, Portland, noted that the study was not a head-to-head trial of polidocanol vs. deoxycholic acid, so he cautioned against drawing strong conclusions about the comparative data presented.

Asked to comment on the results Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, said that 10XB101 “showed excellent efficacy with much fewer adverse events when compared to what we found in studies with Kybella, the only currently FDA-approved injection for submental fat reduction.”

Dr. Green

In addition, “much less pain after injection was to me the most obvious differentiator between this and Kybella studies. I look forward to seeing if larger studies confirm the efficacy and safety from this phase 2 study, as 10XB101 has potential to be a more effective, and safer option to reduce submental fat,” he added. He was not involved with the study.

Dr. Darji reported having no disclosures. Mitchel P. Goldman, MD, the study’s lead investigator, is a minority investor in 10XBio, which is developing 10XB101. Dr. Blauvelt and Dr. Green disclosed conflicts of interest from many pharmaceutical companies.

SAN DIEGO — A novel formulation of polidocanol, an injectable synthetic non-ionic detergent that is approved by the US Food and Drug Administration (FDA) for sclerotherapy, may have a role in excess submental fat reduction, results from a phase 2b trial demonstrated.

The solution, also known as 10XB101, “has been demonstrated to cause adipolysis,” Kavita Darji, MD, an American Society for Dermatologic Surgery (ASDS) cosmetic and dermatologic laser surgery fellow at a practice in San Diego, said during a late-breaking session at the annual meeting of the American Academy of Dermatology. “It shows less inflammation and release of cytokines TNF-alpha and MCP-1 by macrophages than deoxycholic acid, which is currently used for submental fat reduction.”

Dr. Darji

In a phase 2b clinical trial conducted at four sites, investigators enrolled 51 patients and assigned them to one of four dose cohorts: 2%, 3%, or 4.5% 10XB101, or vehicle. Each treatment consisted of up to 50 injections at 0.2 mL per injection, and they were administered up to six times 4 weeks apart. Study endpoints included a composite of the Clinician Submental Fat Score (CSFS) and Patient Submental Fat Score (PSFS) on a 0-4–point scale. The researchers graded local skin reactions such as erythema, edema, tenderness on palpation, bruising, pain, and burning/stinging as 0 (none), 1 (mild), 2 (moderate), or 3 (severe). They also obtained lab tests and performed electrocardiograms.

Dr. Darji and colleagues analyzed two populations: the intent to treat (ITT) population, which included all 51 enrolled subjects who received any injection of the test agent, and a completer population of 40 subjects. “These patients had at least four treatments or completed the treatments per protocol, completed the 4 weeks after final treatment assessments, or did not have any significant protocol deviations that would impact the evaluation of efficacy,” she explained.

To compare how 10XB101 performed compared with deoxycholic acid (Kybella), which is approved by the FDA to improve the appearance of moderate to severe submental fat, the researchers drew from pooled findings of Refine 1 and 2, in which adults received up to six treatment sessions with deoxycholic acid or placebo.

The ITT analysis of the 3% and 4.5% 10XB101 dose groups showed about a fourfold increase in a 2-grade or better improvement in the composite endpoint relative to the pooled findings of deoxycholic acid (62% vs. 16%, respectively). In addition, 80% of the completer population achieved a 2-grade improvement in the composite endpoint. “Importantly, 10% to 33% also received a 3-grade improvement, depending on the dose they were assigned to,” Dr. Darji said.

On average, patients in both cohorts achieved a 1-grade improvement after two treatments, and about 50% achieved a 2-grade improvement after four treatments — which is consistent with a more rapid onset when compared with deoxycholic acid, she said.

Both study endpoints were achieved by 31% of patients in the ITT group vs. 33% of completers, respectively, with the 2% dose; 62% vs. 80% with the 3% dose; and 54% vs. 79% for the 4.5% dose. “This is a 2- to 5-times increase in success” when compared with the results of deoxycholic acid in the published pooled analysis, Dr. Darji said. The researchers measured adverse events by spontaneous and elicited reports and by assessments of recorded local skin reactions. They found that 80% of all measured local skin reactions rated as 0 while 98% of all measured local skin reactions rated as a 0 or 1. One myocardial infarction occurred, which was mild and resolved. This case was not related to the study drug, Dr. Darji said in an interview after the meeting. Otherwise, no safety laboratory or ECG signals were noted.

In findings limited to the 3% dose of 10XB101, mild bruising occurred in 8% of patients at postinjection visit 2, 18% of those at postinjection visit 3, 20% of those at postinjection visit 4, and in 20% of those at postinjection visit 5. Reports of mild pain/burning/stinging occurred in 8% of patients at postinjection visit 2 but at no other subsequent visits. Meanwhile, edema occurred in 42% of patients at postinjection visit 2, 45% of those at postinjection visit 3, 50% of those at postinjection visits 4 and 5, and 38% of those at postinjection visit 6.

“Patients resumed normal activity within 1-3 days and had fewer side effects that lasted longer than 30 days,” Dr. Darji concluded, adding that the results “imply a potential opportunity to expand the treatment to other anatomic areas, which is a future direction.”

One of the session moderators, Andrew Blauvelt, MD, MBA, of Oregon Medical Research Center, Portland, noted that the study was not a head-to-head trial of polidocanol vs. deoxycholic acid, so he cautioned against drawing strong conclusions about the comparative data presented.

Asked to comment on the results Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, said that 10XB101 “showed excellent efficacy with much fewer adverse events when compared to what we found in studies with Kybella, the only currently FDA-approved injection for submental fat reduction.”

Dr. Green

In addition, “much less pain after injection was to me the most obvious differentiator between this and Kybella studies. I look forward to seeing if larger studies confirm the efficacy and safety from this phase 2 study, as 10XB101 has potential to be a more effective, and safer option to reduce submental fat,” he added. He was not involved with the study.

Dr. Darji reported having no disclosures. Mitchel P. Goldman, MD, the study’s lead investigator, is a minority investor in 10XBio, which is developing 10XB101. Dr. Blauvelt and Dr. Green disclosed conflicts of interest from many pharmaceutical companies.

Data from the Minnesota Department of Health (MDH) underscore the often poor reliability of a clinical diagnosis of varicella (chickenpox) in children without laboratory test confirmation, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.

Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
 

Minnesota Offers Free Tests

In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.

MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.

The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).

During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
 

Clinical Diagnosis Versus Lab Test Confirmation

The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.

The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.

They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.

“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
 

Presentation May Also Be Different in Immunocompromised

Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.

In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.

Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.

Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”

But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.

The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.

Data from the Minnesota Department of Health (MDH) underscore the often poor reliability of a clinical diagnosis of varicella (chickenpox) in children without laboratory test confirmation, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.

Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
 

Minnesota Offers Free Tests

In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.

MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.

The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).

During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
 

Clinical Diagnosis Versus Lab Test Confirmation

The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.

The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.

They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.

“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
 

Presentation May Also Be Different in Immunocompromised

Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.

In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.

Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.

Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”

But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.

The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.

Data from the Minnesota Department of Health (MDH) underscore the often poor reliability of a clinical diagnosis of varicella (chickenpox) in children without laboratory test confirmation, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.

Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
 

Minnesota Offers Free Tests

In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.

MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.

The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).

During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
 

Clinical Diagnosis Versus Lab Test Confirmation

The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.

The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.

They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.

“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
 

Presentation May Also Be Different in Immunocompromised

Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.

In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.

Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.

Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”

But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.

The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.