Heartland virus (HRTV), an emerging infection first detected in lone star ticks in Missouri in 2009, has spread to lone star ticks in Georgia, a study published in Emerging Infectious Diseases reports.

HRTV disease is transmitted by the bite of an infected Amblyomma americanum tick, named “lone star” because of the silver-white spot on the female scutum (back).

“By … sampling … in an area with reported exposure to HRTV in wildlife and humans and testing for infection in thousands of ticks from multiple sites and physiologic stages, we confirmed the presence of HRTV in Georgia,” the authors write.

“This information about the expanding geographic range of lone star ticks, combined with increased human presence in tick-infested habitats, can be used to improve strategies for preventing tick bites and to alert physicians about this emerging tickborne virus infection,” a press release by the Centers for Disease Control and Prevention notes.
 

Persistent field and lab work led to HRTV discovery in Georgia

The search for infected lone star ticks began after a retroactive analysis confirmed that a person who died in Georgia in 2005 from an unidentified illness was infected with HRTV. A subsequent analysis of serum samples collected earlier from local white-tailed deer showed that the deer had been exposed to HRTV since at least 2001, according to a press release by Emory University.

These discoveries prompted local researchers to investigate whether lone star ticks in rural, woodsy central Georgia were carrying HRTV.

Lead study author Yamila Romer, MD, an infectious disease clinician and microbiologist in the department of environmental sciences at Emory University in Atlanta, and her colleagues collected samples of ticks in 2018 at 26 sites near the location of the patient who died and the seropositive deer. In 2019, they focused their collections on the two sites that had provided the most ticks in 2018.

From April to October in both years, the research team visited sites weekly to swish white flannel flags through underbrush. They picked off adult and nymph Amblyomma americanum ticks, placed them into vials, and transported them to their lab. They sorted 9,294 ticks by sex, life stage, and collection site. Then they crushed the ticks and extracted their RNA.

To confirm viral infection, the team tested RNA extracted from cell culture supernatants using a real-time polymerase chain reaction test specific for HRTV.

In the three pools of ticks that tested positive for HRTV, the researchers found a minimum infection rate of 0.46/1,000 ticks, suggesting that about 1 of every 2,000 ticks carried HRTV. They sequenced the genome of the three isolates and found that the genomes were similar to one another but were very different from the genomes from HRTV samples taken outside Georgia.

Catherine A. Hill, PhD, a professor of entomology and vector biology and the interim head of the department of entomology at Purdue University in West Lafayette, Ind., was impressed with the researchers’ discovery.

“Heartland virus is difficult to detect,” she said in an email. “The prevalence of human cases is low, and the virus appears to be present at very low levels in populations of lone star tick. The investigators went to some lengths to survey for the virus, collect, and process thousands of ticks – and they found the needle in the haystack.” Dr. Hill was not involved in the study.
 

Georgia data help researchers monitor HRTV spread

HRTV was first identified in 2009 in Missouri in two people hospitalized with fever, muscle pain, diarrhea, and low white blood cell and platelet counts. Researchers traced the infections to lone star ticks, and they found antibodies to the virus in blood samples from deer and other wild mammals.

According to the CDC, U.S. cases of tick-borne diseases more than doubled between 2004 and 2016. As of January 2021, more than 50 human cases of HRTV disease had been reported in 11 Midwestern and Southeastern states: Arkansas, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Missouri, North Carolina, Oklahoma, and Tennessee.
 

Precautions, signs, symptoms, testing, and treatment

“The lone star tick is aggressive and will actively seek out a human host to bite,” Dr. Hill noted.

She recommends that health care providers advise patients to avoid tick habitat, wear protective clothing, apply repellants, know the signs and symptoms of tick-borne disease, and seek immediate medical care if they become ill.

Common symptoms of HRTV disease include fatigue, fever, nausea, diarrhea, and anorexia. Treatment is supportive. Many patients have been hospitalized, and some with comorbidities have died.

HRTV infection is rarely tested for, and the disease burden is unknown. With no commercial tests available in the United States, the CDC performs molecular and serologic testing for HRTV infection. The agency advises doctors to contact their state health department if they suspect a patient may have HRTV disease.
 

Further research is needed

Samantha M. Wisely, PhD, a professor of wildlife ecology and the director of the Cervidae Health Research Initiative at the University of Florida in Gainesville, was not surprised by the study finding.

“The more we look for heartland virus, the more places we find it,” Dr. Wisely told this news organization in an email.

“Little is known about which wildlife play a role in maintaining the virus on the landscape,” said Dr. Wisely, who was not involved in the study. “White-tailed deer have been shown to produce antibodies, meaning they have been exposed to the virus, but no one has actually found the virus in a wildlife species.”

The whole-genome sequencing of the virus was particularly important, Dr. Wisely explained. “Whole-genome data allow researchers to better understand viral evolution, pathogenicity, and viral dynamics across space and time – how it is evolving.”

The study was supported by a grant from the Emory University Research Council. The authors, Dr. Wisely, and Dr. Hill have disclosed no relevant financial relationships.

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

Heartland virus (HRTV), an emerging infection first detected in lone star ticks in Missouri in 2009, has spread to lone star ticks in Georgia, a study published in Emerging Infectious Diseases reports.

HRTV disease is transmitted by the bite of an infected Amblyomma americanum tick, named “lone star” because of the silver-white spot on the female scutum (back).

“By … sampling … in an area with reported exposure to HRTV in wildlife and humans and testing for infection in thousands of ticks from multiple sites and physiologic stages, we confirmed the presence of HRTV in Georgia,” the authors write.

“This information about the expanding geographic range of lone star ticks, combined with increased human presence in tick-infested habitats, can be used to improve strategies for preventing tick bites and to alert physicians about this emerging tickborne virus infection,” a press release by the Centers for Disease Control and Prevention notes.
 

Persistent field and lab work led to HRTV discovery in Georgia

The search for infected lone star ticks began after a retroactive analysis confirmed that a person who died in Georgia in 2005 from an unidentified illness was infected with HRTV. A subsequent analysis of serum samples collected earlier from local white-tailed deer showed that the deer had been exposed to HRTV since at least 2001, according to a press release by Emory University.

These discoveries prompted local researchers to investigate whether lone star ticks in rural, woodsy central Georgia were carrying HRTV.

Lead study author Yamila Romer, MD, an infectious disease clinician and microbiologist in the department of environmental sciences at Emory University in Atlanta, and her colleagues collected samples of ticks in 2018 at 26 sites near the location of the patient who died and the seropositive deer. In 2019, they focused their collections on the two sites that had provided the most ticks in 2018.

From April to October in both years, the research team visited sites weekly to swish white flannel flags through underbrush. They picked off adult and nymph Amblyomma americanum ticks, placed them into vials, and transported them to their lab. They sorted 9,294 ticks by sex, life stage, and collection site. Then they crushed the ticks and extracted their RNA.

To confirm viral infection, the team tested RNA extracted from cell culture supernatants using a real-time polymerase chain reaction test specific for HRTV.

In the three pools of ticks that tested positive for HRTV, the researchers found a minimum infection rate of 0.46/1,000 ticks, suggesting that about 1 of every 2,000 ticks carried HRTV. They sequenced the genome of the three isolates and found that the genomes were similar to one another but were very different from the genomes from HRTV samples taken outside Georgia.

Catherine A. Hill, PhD, a professor of entomology and vector biology and the interim head of the department of entomology at Purdue University in West Lafayette, Ind., was impressed with the researchers’ discovery.

“Heartland virus is difficult to detect,” she said in an email. “The prevalence of human cases is low, and the virus appears to be present at very low levels in populations of lone star tick. The investigators went to some lengths to survey for the virus, collect, and process thousands of ticks – and they found the needle in the haystack.” Dr. Hill was not involved in the study.
 

Georgia data help researchers monitor HRTV spread

HRTV was first identified in 2009 in Missouri in two people hospitalized with fever, muscle pain, diarrhea, and low white blood cell and platelet counts. Researchers traced the infections to lone star ticks, and they found antibodies to the virus in blood samples from deer and other wild mammals.

According to the CDC, U.S. cases of tick-borne diseases more than doubled between 2004 and 2016. As of January 2021, more than 50 human cases of HRTV disease had been reported in 11 Midwestern and Southeastern states: Arkansas, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Missouri, North Carolina, Oklahoma, and Tennessee.
 

Precautions, signs, symptoms, testing, and treatment

“The lone star tick is aggressive and will actively seek out a human host to bite,” Dr. Hill noted.

She recommends that health care providers advise patients to avoid tick habitat, wear protective clothing, apply repellants, know the signs and symptoms of tick-borne disease, and seek immediate medical care if they become ill.

Common symptoms of HRTV disease include fatigue, fever, nausea, diarrhea, and anorexia. Treatment is supportive. Many patients have been hospitalized, and some with comorbidities have died.

HRTV infection is rarely tested for, and the disease burden is unknown. With no commercial tests available in the United States, the CDC performs molecular and serologic testing for HRTV infection. The agency advises doctors to contact their state health department if they suspect a patient may have HRTV disease.
 

Further research is needed

Samantha M. Wisely, PhD, a professor of wildlife ecology and the director of the Cervidae Health Research Initiative at the University of Florida in Gainesville, was not surprised by the study finding.

“The more we look for heartland virus, the more places we find it,” Dr. Wisely told this news organization in an email.

“Little is known about which wildlife play a role in maintaining the virus on the landscape,” said Dr. Wisely, who was not involved in the study. “White-tailed deer have been shown to produce antibodies, meaning they have been exposed to the virus, but no one has actually found the virus in a wildlife species.”

The whole-genome sequencing of the virus was particularly important, Dr. Wisely explained. “Whole-genome data allow researchers to better understand viral evolution, pathogenicity, and viral dynamics across space and time – how it is evolving.”

The study was supported by a grant from the Emory University Research Council. The authors, Dr. Wisely, and Dr. Hill have disclosed no relevant financial relationships.

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

Heartland virus (HRTV), an emerging infection first detected in lone star ticks in Missouri in 2009, has spread to lone star ticks in Georgia, a study published in Emerging Infectious Diseases reports.

HRTV disease is transmitted by the bite of an infected Amblyomma americanum tick, named “lone star” because of the silver-white spot on the female scutum (back).

“By … sampling … in an area with reported exposure to HRTV in wildlife and humans and testing for infection in thousands of ticks from multiple sites and physiologic stages, we confirmed the presence of HRTV in Georgia,” the authors write.

“This information about the expanding geographic range of lone star ticks, combined with increased human presence in tick-infested habitats, can be used to improve strategies for preventing tick bites and to alert physicians about this emerging tickborne virus infection,” a press release by the Centers for Disease Control and Prevention notes.
 

Persistent field and lab work led to HRTV discovery in Georgia

The search for infected lone star ticks began after a retroactive analysis confirmed that a person who died in Georgia in 2005 from an unidentified illness was infected with HRTV. A subsequent analysis of serum samples collected earlier from local white-tailed deer showed that the deer had been exposed to HRTV since at least 2001, according to a press release by Emory University.

These discoveries prompted local researchers to investigate whether lone star ticks in rural, woodsy central Georgia were carrying HRTV.

Lead study author Yamila Romer, MD, an infectious disease clinician and microbiologist in the department of environmental sciences at Emory University in Atlanta, and her colleagues collected samples of ticks in 2018 at 26 sites near the location of the patient who died and the seropositive deer. In 2019, they focused their collections on the two sites that had provided the most ticks in 2018.

From April to October in both years, the research team visited sites weekly to swish white flannel flags through underbrush. They picked off adult and nymph Amblyomma americanum ticks, placed them into vials, and transported them to their lab. They sorted 9,294 ticks by sex, life stage, and collection site. Then they crushed the ticks and extracted their RNA.

To confirm viral infection, the team tested RNA extracted from cell culture supernatants using a real-time polymerase chain reaction test specific for HRTV.

In the three pools of ticks that tested positive for HRTV, the researchers found a minimum infection rate of 0.46/1,000 ticks, suggesting that about 1 of every 2,000 ticks carried HRTV. They sequenced the genome of the three isolates and found that the genomes were similar to one another but were very different from the genomes from HRTV samples taken outside Georgia.

Catherine A. Hill, PhD, a professor of entomology and vector biology and the interim head of the department of entomology at Purdue University in West Lafayette, Ind., was impressed with the researchers’ discovery.

“Heartland virus is difficult to detect,” she said in an email. “The prevalence of human cases is low, and the virus appears to be present at very low levels in populations of lone star tick. The investigators went to some lengths to survey for the virus, collect, and process thousands of ticks – and they found the needle in the haystack.” Dr. Hill was not involved in the study.
 

Georgia data help researchers monitor HRTV spread

HRTV was first identified in 2009 in Missouri in two people hospitalized with fever, muscle pain, diarrhea, and low white blood cell and platelet counts. Researchers traced the infections to lone star ticks, and they found antibodies to the virus in blood samples from deer and other wild mammals.

According to the CDC, U.S. cases of tick-borne diseases more than doubled between 2004 and 2016. As of January 2021, more than 50 human cases of HRTV disease had been reported in 11 Midwestern and Southeastern states: Arkansas, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Missouri, North Carolina, Oklahoma, and Tennessee.
 

Precautions, signs, symptoms, testing, and treatment

“The lone star tick is aggressive and will actively seek out a human host to bite,” Dr. Hill noted.

She recommends that health care providers advise patients to avoid tick habitat, wear protective clothing, apply repellants, know the signs and symptoms of tick-borne disease, and seek immediate medical care if they become ill.

Common symptoms of HRTV disease include fatigue, fever, nausea, diarrhea, and anorexia. Treatment is supportive. Many patients have been hospitalized, and some with comorbidities have died.

HRTV infection is rarely tested for, and the disease burden is unknown. With no commercial tests available in the United States, the CDC performs molecular and serologic testing for HRTV infection. The agency advises doctors to contact their state health department if they suspect a patient may have HRTV disease.
 

Further research is needed

Samantha M. Wisely, PhD, a professor of wildlife ecology and the director of the Cervidae Health Research Initiative at the University of Florida in Gainesville, was not surprised by the study finding.

“The more we look for heartland virus, the more places we find it,” Dr. Wisely told this news organization in an email.

“Little is known about which wildlife play a role in maintaining the virus on the landscape,” said Dr. Wisely, who was not involved in the study. “White-tailed deer have been shown to produce antibodies, meaning they have been exposed to the virus, but no one has actually found the virus in a wildlife species.”

The whole-genome sequencing of the virus was particularly important, Dr. Wisely explained. “Whole-genome data allow researchers to better understand viral evolution, pathogenicity, and viral dynamics across space and time – how it is evolving.”

The study was supported by a grant from the Emory University Research Council. The authors, Dr. Wisely, and Dr. Hill have disclosed no relevant financial relationships.

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

A cell phone rings in a red-brick bungalow in a village in India. A woman on the other end of the phone tells Ms. SK, a community health worker, that menstruation has started. Ms. SK guns her scooter through the dusty streets for 15 minutes in 30° C (86° F) heat.

A 32-year-old woman, waiting in the shade of a blue corrugated-iron roof, hands over a green polythene bag. Ms. SK whisks the package to the local health center and tucks it into a –20° C freezer. The following week, it will ride in dry ice to the National Institute for Research in Reproductive and Child Health Laboratory in Mumbai for human papillomavirus (HPV) testing.

The two women are participants in the world’s first community-based validation trial of cervical screening using menstrual pads.

This moment in rural India at first glance appears to have little relevance to wealthy countries such as the United States.

However, public health officials in both countries are trying to solve the same problem: how to prevent unnecessary deaths from cervical cancer by reaching women who have never or rarely been screened.

The United States has more in common with India than it may care to admit.

“In the U.S., we still have pockets of disparities that actually have incidence rates [of cervical cancer] comparable to many low- and middle-income countries,” said Vikrant Sahasrabuddhe, MBBS, DrPh, MPH, of the National Cancer Institute, where he heads the HPV and cervical cancer prevention clinical research program for the National Institutes of Health.

The incidence of cervical cancer in India is approximately 19 per 100,000 women. For the past 15 years incidence in the United States has stalled at approximately 7 per 100,000.

In India, there are no organized screening programs and most cervical cancer is regional or distant metastatic at diagnosis.

In the United States, 52% of new cases are advanced, and half of these are among women who have never or rarely been screened.

“There is a critical need for new strategies to reach this population,” Dr. Sahasrabuddhe said. “We absolutely have to do something out of the box creatively.”

Almost all cervical cancers are triggered by HPV, most commonly high-risk HPV-16 and HPV-18, although there are more than 200 types. HPV testing is taking over from cytology (Papanicolaou test) for secondary prevention of cervical cancer.

The trial of screening for HPV in menstrual pads that is ongoing in India was the brainchild of Atul Budukh, PhD, a government public health researcher and professor at the Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai.

Dr. Budukh’s eyes were opened to the scale of the problem when he participated in a cluster-randomized trial funded by the Bill and Melinda Gates Foundation. The study, published in 2009 in the New England Journal of Medicine, involved 131,746 rural women in the Osmanabad district of India.

A team of researchers from India and France compared outcomes for women over 8 years after cervical screening by HPV, cytology, or visual inspection with acetic acid. The control group was usual care, where women were advised how to seek screening at local hospitals. Women who screened positive were referred for colposcopy, biopsy, and treatment.

Over the 8-year follow-up, advanced cervical cancer was found in twice as many women left to their own devices, compared with women who had HPV testing during the study (82 vs. 39; hazard ratio for HPV, 0.47; 95% confidence interval, 0.32-0.69).

Similarly, cervical cancer deaths in the control group were nearly two times higher than among the women who were screened for HPV in the study (64 vs. 34; HR for HPV, 0.52; 95% CI, 0.33-0.83).

The study proved that rural Indian women were dying unnecessarily because they weren’t seeking cervical screening. And education wasn’t the problem.

“When we go and educate [a rural woman] about ... risk factors and the need to undergo screening, she understands it very well,” said Dr. Budukh. “She is ready to come but her priority is her bread and butter – she will lose her daily wages.”

Dr. Budukh and his team negotiated with local employers so that women could come to screening clinics, but they soon realized this wasn’t scalable.

One year after the NEJM publication, Dr. Budukh found what he was looking for.

A team of Hong Kong clinicians, headed by Sze Chuen Cesar Wong of the Hong Kong Cancer Institute, published a paper in 2010 in the Journal of Clinical Microbiology showing that menstrual pads provide reliable HPV results in women with and without cervical disease.

The Hong Kong team tested sanitary napkins for HPV from 235 of their patients with cervical intraepithelial neoplasia or condyloma acuminatum before and after treatment. Samples were compared with those from 323 women without cervical disease; for HPV in sanitary napkins the sensitivity was 82.8%, specificity was 93.1%, and positive and negative predictive values were 90% and 87.9%, respectively.

The authors pointed out that menstrual pad testing was the only truly noninvasive approach to HPV screening versus the other self-sampling methods such as tampons and cytobrushes. Also, these self-sampling tests require specialized liquid-based transport media. A menstrual pad needs only a plastic bag.

Dr. Budukh had his at-home solution for the hard-working rural women of India.

With funding from the Indian government, Dr. Budukh’s team put together a validation trial that ran from 2013 to 2016 in 18 rural villages in two separate districts: Ahmednagar and Pune.

Local health workers went house to house to recruit women and get family buy-in for this culturally delicate project. Participants were instructed to use their regular sanitary protection – most commonly a washable cloth – and told to call the health worker on the first day of menstruation. Health workers gave each woman a Ziploc bag for the pad and, for privacy, an outer polythene sac.

In Ahmednagar, all women who provided their pad also got screened with Hybrid Capture 2 (HC2; Qiagen) by a mobile screening unit. In Pune, only the positive cases underwent HC2. Screening was also extended to anyone who requested it, but these people were not included in the final analysis.

Genomic DNA was extracted from three 5 mm–sized punches in the pad using a commercial kit, QIAamp DNA Micro, and the quality and purity of the DNA checked by Implen NanoPhotometer.

The team followed the same protocol for PCR HPV assay as the team from Hong Kong.

The results were published in the European Journal of Cancer Prevention in 2018.

The concordance rate for a positive result between the menstrual pad sample and conventional HPV sampling was 98.8% for Ahmednagar and 95.2% for samples from Pune. The sensitivity for the first study was 83% and the specificity 99% – similar to that for the women in Hong Kong. The second study had lower sensitivity and specificity (67% and 88%), partly because of poor storage as a result of frequent power cuts.

The total cost per woman was $30.78.

“I was very excited when we saw the results,” Dr. Budukh recalled. “That day I couldn’t sleep ... such a wonderful result! I was excited to start the next phase immediately.”

Dr. Budukh has applied to the Indian government for funding for a larger trial involving 3,000 women. If successful, he hopes such evidence would be sufficient to convince the Indian government to make menstrual pad screening standard procedure for the 390 million women who live in India’s countryside.

Testing never-screened women for cervical cancer using menstrual pads appears to be relatively reliable, convenient, private, noninvasive, and incredibly cheap.

So who else has tried it?

The first published account of HPV in menstrual blood was a 2003 study by Tommy Tong and colleagues at the Princess Margaret Hospital in Hong Kong. The authors heralded, with lamentable optimism, “a new paradigm in cervical cancer screening.”

In the following 20 years, just six more studies appeared: two from Dr. Budukh’s field trial in India and four from hospital-based pilot studies in Hong Kong (in 2010 and 2018), South Korea (in 2016), and mainland China (in 2021). All these studies, although small, were published in top-flight journals and demonstrate high concordance between conventional high-risk HPV testing and menstrual-blood tests.

This news organization tried to find a U.S. thought-leader who had heard of the approach.

Elizabeth Fontham, MPH, DrPh, is the founding dean of the school of public health at Louisiana State University Health Center in New Orleans, and president of the American Cancer Society. Dr. Fontham said in an email that she had “no plans to evaluate the impact related to menstrual pads, but perhaps others have looked into that.”

Joy Melnikow, MD, MPH, was first author on the evidence synthesis driving the current cervical cancer screening recommendations from the U.S. Preventive Services Task Force. When asked about menstrual pad testing for HPV, she said she had “not heard of it before.”

The USPSTF guidelines don’t mention sanitary pads but acknowledge that “self-collection may be one strategy for increasing screening rates among populations where they are currently low.”

The USPSTF methodology excludes data from countries that don’t match the United States on the Human Development Index “or [are] not applicable to U.S. clinical settings or populations.” (Presumably, data from Hong Kong and South Korea would qualify; Indian data would not.)

Dr. Sahasrabuddhe of the NCI hadn’t heard of menstrual pad testing either, but he has a different explanation for lack of interest in this approach – or, indeed, any form of self-sampling for cervical cancer screening – in the United States.

“We have not seen movement happen in this space for years. ... If there is one intervention that we can simplify, that still has not been made widely available, it is self-sampling ... [but] we don’t have [Food and Drug Administration] approval for it,” Dr. Sahasrabuddhe said.

“Our system, at least in the U.S., is based on industry manufacturers seeking an approval for a particular way of collection and then clinicians and clinical-guideline bodies signing on. ... For a lot of reasons industry has shied away over the past several years, so far, at least, on seeking approval for self-sampling-based approaches,” he commented.

Dr. Sahasrabuddhe aims to change that. He heads a new NCI-led initiative called “The Last Mile,” a nationwide clinical trial supported by federal agencies, industry partners, and professional societies. The goal is to validate self-sampled HPV testing as non-inferior to specimens collected by providers. The team is currently finalizing the methodology of the study, so Dr. Sahasrabuddhe could not share the self-sampling methods that will be on trial, nor the industry partners who have signed up.

The following tests are approved in the United States for physician-collected HPV screening: Hybrid Capture 2, used in the Indian studies (Qiagen); cobas HPV (Roche); Aptima (Hologic); Cervista (Hologic); and Onclarity (Becton Dickinson).

Dr. Sahasrabuddhe said that, while a sanitary pad in a Ziploc bag is unlikely to make the grade for The Last Mile study, he doesn’t totally dismiss their potential and said the NCI is always open to new ideas.

“We are not supporting anybody specifically for menstrual pad-based collection device development,” Dr. Sahasrabuddhe said, “But if they fulfill other criteria for a small business–based grant application, they absolutely are welcome to apply for NCI funding for this.”

Said Dr. Melnikow: “Pre-COVID, the head of [the World Health Organization] said that we could eliminate cervical cancer from the globe and that we have the tools to do that now. And he’s right.”

Dr. Budukh, Dr. Melnikow, and Dr. Sahasrabuddhe disclosed no relevant financial relationships.

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

A cell phone rings in a red-brick bungalow in a village in India. A woman on the other end of the phone tells Ms. SK, a community health worker, that menstruation has started. Ms. SK guns her scooter through the dusty streets for 15 minutes in 30° C (86° F) heat.

A 32-year-old woman, waiting in the shade of a blue corrugated-iron roof, hands over a green polythene bag. Ms. SK whisks the package to the local health center and tucks it into a –20° C freezer. The following week, it will ride in dry ice to the National Institute for Research in Reproductive and Child Health Laboratory in Mumbai for human papillomavirus (HPV) testing.

The two women are participants in the world’s first community-based validation trial of cervical screening using menstrual pads.

This moment in rural India at first glance appears to have little relevance to wealthy countries such as the United States.

However, public health officials in both countries are trying to solve the same problem: how to prevent unnecessary deaths from cervical cancer by reaching women who have never or rarely been screened.

The United States has more in common with India than it may care to admit.

“In the U.S., we still have pockets of disparities that actually have incidence rates [of cervical cancer] comparable to many low- and middle-income countries,” said Vikrant Sahasrabuddhe, MBBS, DrPh, MPH, of the National Cancer Institute, where he heads the HPV and cervical cancer prevention clinical research program for the National Institutes of Health.

The incidence of cervical cancer in India is approximately 19 per 100,000 women. For the past 15 years incidence in the United States has stalled at approximately 7 per 100,000.

In India, there are no organized screening programs and most cervical cancer is regional or distant metastatic at diagnosis.

In the United States, 52% of new cases are advanced, and half of these are among women who have never or rarely been screened.

“There is a critical need for new strategies to reach this population,” Dr. Sahasrabuddhe said. “We absolutely have to do something out of the box creatively.”

Almost all cervical cancers are triggered by HPV, most commonly high-risk HPV-16 and HPV-18, although there are more than 200 types. HPV testing is taking over from cytology (Papanicolaou test) for secondary prevention of cervical cancer.

The trial of screening for HPV in menstrual pads that is ongoing in India was the brainchild of Atul Budukh, PhD, a government public health researcher and professor at the Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai.

Dr. Budukh’s eyes were opened to the scale of the problem when he participated in a cluster-randomized trial funded by the Bill and Melinda Gates Foundation. The study, published in 2009 in the New England Journal of Medicine, involved 131,746 rural women in the Osmanabad district of India.

A team of researchers from India and France compared outcomes for women over 8 years after cervical screening by HPV, cytology, or visual inspection with acetic acid. The control group was usual care, where women were advised how to seek screening at local hospitals. Women who screened positive were referred for colposcopy, biopsy, and treatment.

Over the 8-year follow-up, advanced cervical cancer was found in twice as many women left to their own devices, compared with women who had HPV testing during the study (82 vs. 39; hazard ratio for HPV, 0.47; 95% confidence interval, 0.32-0.69).

Similarly, cervical cancer deaths in the control group were nearly two times higher than among the women who were screened for HPV in the study (64 vs. 34; HR for HPV, 0.52; 95% CI, 0.33-0.83).

The study proved that rural Indian women were dying unnecessarily because they weren’t seeking cervical screening. And education wasn’t the problem.

“When we go and educate [a rural woman] about ... risk factors and the need to undergo screening, she understands it very well,” said Dr. Budukh. “She is ready to come but her priority is her bread and butter – she will lose her daily wages.”

Dr. Budukh and his team negotiated with local employers so that women could come to screening clinics, but they soon realized this wasn’t scalable.

One year after the NEJM publication, Dr. Budukh found what he was looking for.

A team of Hong Kong clinicians, headed by Sze Chuen Cesar Wong of the Hong Kong Cancer Institute, published a paper in 2010 in the Journal of Clinical Microbiology showing that menstrual pads provide reliable HPV results in women with and without cervical disease.

The Hong Kong team tested sanitary napkins for HPV from 235 of their patients with cervical intraepithelial neoplasia or condyloma acuminatum before and after treatment. Samples were compared with those from 323 women without cervical disease; for HPV in sanitary napkins the sensitivity was 82.8%, specificity was 93.1%, and positive and negative predictive values were 90% and 87.9%, respectively.

The authors pointed out that menstrual pad testing was the only truly noninvasive approach to HPV screening versus the other self-sampling methods such as tampons and cytobrushes. Also, these self-sampling tests require specialized liquid-based transport media. A menstrual pad needs only a plastic bag.

Dr. Budukh had his at-home solution for the hard-working rural women of India.

With funding from the Indian government, Dr. Budukh’s team put together a validation trial that ran from 2013 to 2016 in 18 rural villages in two separate districts: Ahmednagar and Pune.

Local health workers went house to house to recruit women and get family buy-in for this culturally delicate project. Participants were instructed to use their regular sanitary protection – most commonly a washable cloth – and told to call the health worker on the first day of menstruation. Health workers gave each woman a Ziploc bag for the pad and, for privacy, an outer polythene sac.

In Ahmednagar, all women who provided their pad also got screened with Hybrid Capture 2 (HC2; Qiagen) by a mobile screening unit. In Pune, only the positive cases underwent HC2. Screening was also extended to anyone who requested it, but these people were not included in the final analysis.

Genomic DNA was extracted from three 5 mm–sized punches in the pad using a commercial kit, QIAamp DNA Micro, and the quality and purity of the DNA checked by Implen NanoPhotometer.

The team followed the same protocol for PCR HPV assay as the team from Hong Kong.

The results were published in the European Journal of Cancer Prevention in 2018.

The concordance rate for a positive result between the menstrual pad sample and conventional HPV sampling was 98.8% for Ahmednagar and 95.2% for samples from Pune. The sensitivity for the first study was 83% and the specificity 99% – similar to that for the women in Hong Kong. The second study had lower sensitivity and specificity (67% and 88%), partly because of poor storage as a result of frequent power cuts.

The total cost per woman was $30.78.

“I was very excited when we saw the results,” Dr. Budukh recalled. “That day I couldn’t sleep ... such a wonderful result! I was excited to start the next phase immediately.”

Dr. Budukh has applied to the Indian government for funding for a larger trial involving 3,000 women. If successful, he hopes such evidence would be sufficient to convince the Indian government to make menstrual pad screening standard procedure for the 390 million women who live in India’s countryside.

Testing never-screened women for cervical cancer using menstrual pads appears to be relatively reliable, convenient, private, noninvasive, and incredibly cheap.

So who else has tried it?

The first published account of HPV in menstrual blood was a 2003 study by Tommy Tong and colleagues at the Princess Margaret Hospital in Hong Kong. The authors heralded, with lamentable optimism, “a new paradigm in cervical cancer screening.”

In the following 20 years, just six more studies appeared: two from Dr. Budukh’s field trial in India and four from hospital-based pilot studies in Hong Kong (in 2010 and 2018), South Korea (in 2016), and mainland China (in 2021). All these studies, although small, were published in top-flight journals and demonstrate high concordance between conventional high-risk HPV testing and menstrual-blood tests.

This news organization tried to find a U.S. thought-leader who had heard of the approach.

Elizabeth Fontham, MPH, DrPh, is the founding dean of the school of public health at Louisiana State University Health Center in New Orleans, and president of the American Cancer Society. Dr. Fontham said in an email that she had “no plans to evaluate the impact related to menstrual pads, but perhaps others have looked into that.”

Joy Melnikow, MD, MPH, was first author on the evidence synthesis driving the current cervical cancer screening recommendations from the U.S. Preventive Services Task Force. When asked about menstrual pad testing for HPV, she said she had “not heard of it before.”

The USPSTF guidelines don’t mention sanitary pads but acknowledge that “self-collection may be one strategy for increasing screening rates among populations where they are currently low.”

The USPSTF methodology excludes data from countries that don’t match the United States on the Human Development Index “or [are] not applicable to U.S. clinical settings or populations.” (Presumably, data from Hong Kong and South Korea would qualify; Indian data would not.)

Dr. Sahasrabuddhe of the NCI hadn’t heard of menstrual pad testing either, but he has a different explanation for lack of interest in this approach – or, indeed, any form of self-sampling for cervical cancer screening – in the United States.

“We have not seen movement happen in this space for years. ... If there is one intervention that we can simplify, that still has not been made widely available, it is self-sampling ... [but] we don’t have [Food and Drug Administration] approval for it,” Dr. Sahasrabuddhe said.

“Our system, at least in the U.S., is based on industry manufacturers seeking an approval for a particular way of collection and then clinicians and clinical-guideline bodies signing on. ... For a lot of reasons industry has shied away over the past several years, so far, at least, on seeking approval for self-sampling-based approaches,” he commented.

Dr. Sahasrabuddhe aims to change that. He heads a new NCI-led initiative called “The Last Mile,” a nationwide clinical trial supported by federal agencies, industry partners, and professional societies. The goal is to validate self-sampled HPV testing as non-inferior to specimens collected by providers. The team is currently finalizing the methodology of the study, so Dr. Sahasrabuddhe could not share the self-sampling methods that will be on trial, nor the industry partners who have signed up.

The following tests are approved in the United States for physician-collected HPV screening: Hybrid Capture 2, used in the Indian studies (Qiagen); cobas HPV (Roche); Aptima (Hologic); Cervista (Hologic); and Onclarity (Becton Dickinson).

Dr. Sahasrabuddhe said that, while a sanitary pad in a Ziploc bag is unlikely to make the grade for The Last Mile study, he doesn’t totally dismiss their potential and said the NCI is always open to new ideas.

“We are not supporting anybody specifically for menstrual pad-based collection device development,” Dr. Sahasrabuddhe said, “But if they fulfill other criteria for a small business–based grant application, they absolutely are welcome to apply for NCI funding for this.”

Said Dr. Melnikow: “Pre-COVID, the head of [the World Health Organization] said that we could eliminate cervical cancer from the globe and that we have the tools to do that now. And he’s right.”

Dr. Budukh, Dr. Melnikow, and Dr. Sahasrabuddhe disclosed no relevant financial relationships.

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

A cell phone rings in a red-brick bungalow in a village in India. A woman on the other end of the phone tells Ms. SK, a community health worker, that menstruation has started. Ms. SK guns her scooter through the dusty streets for 15 minutes in 30° C (86° F) heat.

A 32-year-old woman, waiting in the shade of a blue corrugated-iron roof, hands over a green polythene bag. Ms. SK whisks the package to the local health center and tucks it into a –20° C freezer. The following week, it will ride in dry ice to the National Institute for Research in Reproductive and Child Health Laboratory in Mumbai for human papillomavirus (HPV) testing.

The two women are participants in the world’s first community-based validation trial of cervical screening using menstrual pads.

This moment in rural India at first glance appears to have little relevance to wealthy countries such as the United States.

However, public health officials in both countries are trying to solve the same problem: how to prevent unnecessary deaths from cervical cancer by reaching women who have never or rarely been screened.

The United States has more in common with India than it may care to admit.

“In the U.S., we still have pockets of disparities that actually have incidence rates [of cervical cancer] comparable to many low- and middle-income countries,” said Vikrant Sahasrabuddhe, MBBS, DrPh, MPH, of the National Cancer Institute, where he heads the HPV and cervical cancer prevention clinical research program for the National Institutes of Health.

The incidence of cervical cancer in India is approximately 19 per 100,000 women. For the past 15 years incidence in the United States has stalled at approximately 7 per 100,000.

In India, there are no organized screening programs and most cervical cancer is regional or distant metastatic at diagnosis.

In the United States, 52% of new cases are advanced, and half of these are among women who have never or rarely been screened.

“There is a critical need for new strategies to reach this population,” Dr. Sahasrabuddhe said. “We absolutely have to do something out of the box creatively.”

Almost all cervical cancers are triggered by HPV, most commonly high-risk HPV-16 and HPV-18, although there are more than 200 types. HPV testing is taking over from cytology (Papanicolaou test) for secondary prevention of cervical cancer.

The trial of screening for HPV in menstrual pads that is ongoing in India was the brainchild of Atul Budukh, PhD, a government public health researcher and professor at the Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai.

Dr. Budukh’s eyes were opened to the scale of the problem when he participated in a cluster-randomized trial funded by the Bill and Melinda Gates Foundation. The study, published in 2009 in the New England Journal of Medicine, involved 131,746 rural women in the Osmanabad district of India.

A team of researchers from India and France compared outcomes for women over 8 years after cervical screening by HPV, cytology, or visual inspection with acetic acid. The control group was usual care, where women were advised how to seek screening at local hospitals. Women who screened positive were referred for colposcopy, biopsy, and treatment.

Over the 8-year follow-up, advanced cervical cancer was found in twice as many women left to their own devices, compared with women who had HPV testing during the study (82 vs. 39; hazard ratio for HPV, 0.47; 95% confidence interval, 0.32-0.69).

Similarly, cervical cancer deaths in the control group were nearly two times higher than among the women who were screened for HPV in the study (64 vs. 34; HR for HPV, 0.52; 95% CI, 0.33-0.83).

The study proved that rural Indian women were dying unnecessarily because they weren’t seeking cervical screening. And education wasn’t the problem.

“When we go and educate [a rural woman] about ... risk factors and the need to undergo screening, she understands it very well,” said Dr. Budukh. “She is ready to come but her priority is her bread and butter – she will lose her daily wages.”

Dr. Budukh and his team negotiated with local employers so that women could come to screening clinics, but they soon realized this wasn’t scalable.

One year after the NEJM publication, Dr. Budukh found what he was looking for.

A team of Hong Kong clinicians, headed by Sze Chuen Cesar Wong of the Hong Kong Cancer Institute, published a paper in 2010 in the Journal of Clinical Microbiology showing that menstrual pads provide reliable HPV results in women with and without cervical disease.

The Hong Kong team tested sanitary napkins for HPV from 235 of their patients with cervical intraepithelial neoplasia or condyloma acuminatum before and after treatment. Samples were compared with those from 323 women without cervical disease; for HPV in sanitary napkins the sensitivity was 82.8%, specificity was 93.1%, and positive and negative predictive values were 90% and 87.9%, respectively.

The authors pointed out that menstrual pad testing was the only truly noninvasive approach to HPV screening versus the other self-sampling methods such as tampons and cytobrushes. Also, these self-sampling tests require specialized liquid-based transport media. A menstrual pad needs only a plastic bag.

Dr. Budukh had his at-home solution for the hard-working rural women of India.

With funding from the Indian government, Dr. Budukh’s team put together a validation trial that ran from 2013 to 2016 in 18 rural villages in two separate districts: Ahmednagar and Pune.

Local health workers went house to house to recruit women and get family buy-in for this culturally delicate project. Participants were instructed to use their regular sanitary protection – most commonly a washable cloth – and told to call the health worker on the first day of menstruation. Health workers gave each woman a Ziploc bag for the pad and, for privacy, an outer polythene sac.

In Ahmednagar, all women who provided their pad also got screened with Hybrid Capture 2 (HC2; Qiagen) by a mobile screening unit. In Pune, only the positive cases underwent HC2. Screening was also extended to anyone who requested it, but these people were not included in the final analysis.

Genomic DNA was extracted from three 5 mm–sized punches in the pad using a commercial kit, QIAamp DNA Micro, and the quality and purity of the DNA checked by Implen NanoPhotometer.

The team followed the same protocol for PCR HPV assay as the team from Hong Kong.

The results were published in the European Journal of Cancer Prevention in 2018.

The concordance rate for a positive result between the menstrual pad sample and conventional HPV sampling was 98.8% for Ahmednagar and 95.2% for samples from Pune. The sensitivity for the first study was 83% and the specificity 99% – similar to that for the women in Hong Kong. The second study had lower sensitivity and specificity (67% and 88%), partly because of poor storage as a result of frequent power cuts.

The total cost per woman was $30.78.

“I was very excited when we saw the results,” Dr. Budukh recalled. “That day I couldn’t sleep ... such a wonderful result! I was excited to start the next phase immediately.”

Dr. Budukh has applied to the Indian government for funding for a larger trial involving 3,000 women. If successful, he hopes such evidence would be sufficient to convince the Indian government to make menstrual pad screening standard procedure for the 390 million women who live in India’s countryside.

Testing never-screened women for cervical cancer using menstrual pads appears to be relatively reliable, convenient, private, noninvasive, and incredibly cheap.

So who else has tried it?

The first published account of HPV in menstrual blood was a 2003 study by Tommy Tong and colleagues at the Princess Margaret Hospital in Hong Kong. The authors heralded, with lamentable optimism, “a new paradigm in cervical cancer screening.”

In the following 20 years, just six more studies appeared: two from Dr. Budukh’s field trial in India and four from hospital-based pilot studies in Hong Kong (in 2010 and 2018), South Korea (in 2016), and mainland China (in 2021). All these studies, although small, were published in top-flight journals and demonstrate high concordance between conventional high-risk HPV testing and menstrual-blood tests.

This news organization tried to find a U.S. thought-leader who had heard of the approach.

Elizabeth Fontham, MPH, DrPh, is the founding dean of the school of public health at Louisiana State University Health Center in New Orleans, and president of the American Cancer Society. Dr. Fontham said in an email that she had “no plans to evaluate the impact related to menstrual pads, but perhaps others have looked into that.”

Joy Melnikow, MD, MPH, was first author on the evidence synthesis driving the current cervical cancer screening recommendations from the U.S. Preventive Services Task Force. When asked about menstrual pad testing for HPV, she said she had “not heard of it before.”

The USPSTF guidelines don’t mention sanitary pads but acknowledge that “self-collection may be one strategy for increasing screening rates among populations where they are currently low.”

The USPSTF methodology excludes data from countries that don’t match the United States on the Human Development Index “or [are] not applicable to U.S. clinical settings or populations.” (Presumably, data from Hong Kong and South Korea would qualify; Indian data would not.)

Dr. Sahasrabuddhe of the NCI hadn’t heard of menstrual pad testing either, but he has a different explanation for lack of interest in this approach – or, indeed, any form of self-sampling for cervical cancer screening – in the United States.

“We have not seen movement happen in this space for years. ... If there is one intervention that we can simplify, that still has not been made widely available, it is self-sampling ... [but] we don’t have [Food and Drug Administration] approval for it,” Dr. Sahasrabuddhe said.

“Our system, at least in the U.S., is based on industry manufacturers seeking an approval for a particular way of collection and then clinicians and clinical-guideline bodies signing on. ... For a lot of reasons industry has shied away over the past several years, so far, at least, on seeking approval for self-sampling-based approaches,” he commented.

Dr. Sahasrabuddhe aims to change that. He heads a new NCI-led initiative called “The Last Mile,” a nationwide clinical trial supported by federal agencies, industry partners, and professional societies. The goal is to validate self-sampled HPV testing as non-inferior to specimens collected by providers. The team is currently finalizing the methodology of the study, so Dr. Sahasrabuddhe could not share the self-sampling methods that will be on trial, nor the industry partners who have signed up.

The following tests are approved in the United States for physician-collected HPV screening: Hybrid Capture 2, used in the Indian studies (Qiagen); cobas HPV (Roche); Aptima (Hologic); Cervista (Hologic); and Onclarity (Becton Dickinson).

Dr. Sahasrabuddhe said that, while a sanitary pad in a Ziploc bag is unlikely to make the grade for The Last Mile study, he doesn’t totally dismiss their potential and said the NCI is always open to new ideas.

“We are not supporting anybody specifically for menstrual pad-based collection device development,” Dr. Sahasrabuddhe said, “But if they fulfill other criteria for a small business–based grant application, they absolutely are welcome to apply for NCI funding for this.”

Said Dr. Melnikow: “Pre-COVID, the head of [the World Health Organization] said that we could eliminate cervical cancer from the globe and that we have the tools to do that now. And he’s right.”

Dr. Budukh, Dr. Melnikow, and Dr. Sahasrabuddhe disclosed no relevant financial relationships.

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

_{Text copyright DenseBreast-info.org.}

Answer

B.  The Gail risk model^1-3 is used to predict 5-year and lifetime risks of developing invasive breast cancer, and to identify women who may benefit from risk-reducing medications such as tamoxifen. The Gail model should not be used to determine risk for purposes of screening magnetic resonance imaging (MRI)⁴ (or genetic testing).

Breast cancer risk models are used to stratify patients into risk categories to facilitate personalized screening and surveillance plans for clinical management. Several breast cancer risk assessment tools have been developed that include different combinations of known risk factors and are used for the following purposes: 

1. To identify women who may benefit from risk-reducing medications. The Gail model is used to determine risk for purposes of advising on use of risk-reducing medications. Any woman with a 5-year risk ≥1.67% by the Gail model may be considered for treatment with tamoxifen (pre or postmenopausal), raloxifene (postmenopausal), or aromatase inhibitors (postmenopausal).⁵  

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 study,⁶ women at increased risk for breast cancer were defined as follows: 

• age 35 to 59 years with at least a 1.66% 5-year risk for developing breast cancer by the Gail model
• personal history of lobular carcinoma in situ (LCIS)
• age over 60 years.

More than 13,000 such women were randomly assigned to receive tamoxifen or placebo daily for 5 years. Tamoxifen reduced the risk of invasive breast cancer by 49% and reduced the risk of noninvasive cancer by 50% compared with placebo. The reduced risk of breast cancer was only seen for estrogen-receptor–expressing tumors. There was a 2.5-fold increase in risk of endometrial cancer in women taking tamoxifen and a decrease in hip and spine fracture risk. Blood clots causing stroke and deep vein thrombosis are increased in women taking tamoxifen.^7,8

2. To identify women who may carry a pathogenic mutation in BRCA1 or BRCA2. Some models (eg, Tyrer-Cuzick [IBIS],⁹ Penn II,¹⁰ BOADICEA,¹¹ and BRCAPRO¹²) estimate the probability of a BRCA1/2 mutation; however, most testing guidelines are now criterion based (eg, National Comprehensive Cancer Network [NCCN]) as opposed to probability based. In practical terms, clinical decision making around genetic testing is rarely based on a priori probabilities. 

3.  To identify women who meet criteria for high-risk screening MRI. Current American Cancer Society (ACS) guidelines⁴ recommend annual screening MRI, in addition to mammography, beginning by age 25 to 30 in women who have a lifetime risk of breast cancer ≥20%. Any of the models used to predict risk of a pathogenic mutation (Tyrer-Cuzick [IBIS], Penn II, BOADICEA, BRCAPRO),or the Claus model,¹³ but not the Gail model, can be used to estimate lifetime risk for purposes of screening MRI guidelines. The ACS and NCCN guidelines specifically recommend against using the Gail model to determine risk for purposes of MRI screening or risk of pathogenic mutation, as it does not include detailed family history such as age at diagnosis or second-degree relatives. 

ACS and NCCN guidelines also recommend annual screening MRI beginning by age 25, with the addition of mammography beginning at age 30, in women who are known to carry pathogenic mutations in BRCA1 or BRCA2 (unless the woman has had bilateral mastectomy), and in women who are first-degree relatives of known mutation carriers but who are themselves untested.¹⁴ 

Women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations (such as those associated with Li-Fraumeni syndrome, Bannayan-Riley-Ruvalcaba syndrome, hereditary diffuse gastric cancer, Peutz-Jeghers syndrome, Cowden syndrome, Neurofibromatosis type 1, or Fanconi anemia) are also recommended for annual screening MRI beginning between ages 20-35, depending on the mutation.¹⁴ Women with known pathogenic mutations in ATM, CHEK2, or NBN should consider annual MRI starting at age 40 or 5-10 years before the earliest known breast cancer in the family (whichever comes first). 

Finally, women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer,^4,15,16 with risk similar in magnitude to pathogenic BRCA1 or BRCA2  carriers. These women are also recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.

Currently the Tyrer-Cuzick Model (IBIS) version 817 and the Breast Cancer Surveillance Consortium (BCSC) models¹⁸ include breast density in risk calculations; the Gail, Penn II, and Claus models do not include breast density. 

Adding polygenic risk scores based on single nucleotide polymorphisms to traditional comprehensive risk models such as the Tyrer-Cuzick model has been shown to improve model performance.¹⁹ In addition, artificial intelligence is being used to identify textural and other findings beyond breast density on mammograms that predict increased risk. Such information, which is complementary to the Tyrer-Cuzick model (v.8),²⁰ has more accurately identified high-risk patients than the Tyrer-Cuzick v8 risk model and prior deep learning models.²¹ 

In a study from the Karolinska Institute, a model that included computer-aided detection of microcalcifications and masses in addition to other traditional risk factors (including breast density) successfully identified women who would develop interval or advanced cancer in the 2 years after a normal mammogram and improved short-term (2-to-3-year) risk assessment over TyrerCuzick (v.7) or Gail models.²² This model proved more accurate than traditional risk models and can augment genetic/family history to help identify women who should and, importantly, who should not, have supplemental screening after 2D mammography. Risk models that include detailed family history should be used rather than the Gail model to identify women who meet high risk criteria for MRI screening. Research also supports the benefits of MRI in women with dense breasts who are not otherwise considered “high risk,” and while not widely available, lower cost, abbreviated MRI protocols have been validated for all women with dense breasts.²³ For more details on risk models, including a risk models table with live links to commonly used breast cancer risk assessment tools, visit https://densebreast-info .org/for-providers/risk-model-tutorial/. ●

_{Text copyright DenseBreast-info.org.}

Answer

B.  The Gail risk model^1-3 is used to predict 5-year and lifetime risks of developing invasive breast cancer, and to identify women who may benefit from risk-reducing medications such as tamoxifen. The Gail model should not be used to determine risk for purposes of screening magnetic resonance imaging (MRI)⁴ (or genetic testing).

Breast cancer risk models are used to stratify patients into risk categories to facilitate personalized screening and surveillance plans for clinical management. Several breast cancer risk assessment tools have been developed that include different combinations of known risk factors and are used for the following purposes: 

1. To identify women who may benefit from risk-reducing medications. The Gail model is used to determine risk for purposes of advising on use of risk-reducing medications. Any woman with a 5-year risk ≥1.67% by the Gail model may be considered for treatment with tamoxifen (pre or postmenopausal), raloxifene (postmenopausal), or aromatase inhibitors (postmenopausal).⁵  

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 study,⁶ women at increased risk for breast cancer were defined as follows: 

• age 35 to 59 years with at least a 1.66% 5-year risk for developing breast cancer by the Gail model
• personal history of lobular carcinoma in situ (LCIS)
• age over 60 years.

More than 13,000 such women were randomly assigned to receive tamoxifen or placebo daily for 5 years. Tamoxifen reduced the risk of invasive breast cancer by 49% and reduced the risk of noninvasive cancer by 50% compared with placebo. The reduced risk of breast cancer was only seen for estrogen-receptor–expressing tumors. There was a 2.5-fold increase in risk of endometrial cancer in women taking tamoxifen and a decrease in hip and spine fracture risk. Blood clots causing stroke and deep vein thrombosis are increased in women taking tamoxifen.^7,8

2. To identify women who may carry a pathogenic mutation in BRCA1 or BRCA2. Some models (eg, Tyrer-Cuzick [IBIS],⁹ Penn II,¹⁰ BOADICEA,¹¹ and BRCAPRO¹²) estimate the probability of a BRCA1/2 mutation; however, most testing guidelines are now criterion based (eg, National Comprehensive Cancer Network [NCCN]) as opposed to probability based. In practical terms, clinical decision making around genetic testing is rarely based on a priori probabilities. 

3.  To identify women who meet criteria for high-risk screening MRI. Current American Cancer Society (ACS) guidelines⁴ recommend annual screening MRI, in addition to mammography, beginning by age 25 to 30 in women who have a lifetime risk of breast cancer ≥20%. Any of the models used to predict risk of a pathogenic mutation (Tyrer-Cuzick [IBIS], Penn II, BOADICEA, BRCAPRO),or the Claus model,¹³ but not the Gail model, can be used to estimate lifetime risk for purposes of screening MRI guidelines. The ACS and NCCN guidelines specifically recommend against using the Gail model to determine risk for purposes of MRI screening or risk of pathogenic mutation, as it does not include detailed family history such as age at diagnosis or second-degree relatives. 

ACS and NCCN guidelines also recommend annual screening MRI beginning by age 25, with the addition of mammography beginning at age 30, in women who are known to carry pathogenic mutations in BRCA1 or BRCA2 (unless the woman has had bilateral mastectomy), and in women who are first-degree relatives of known mutation carriers but who are themselves untested.¹⁴ 

Women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations (such as those associated with Li-Fraumeni syndrome, Bannayan-Riley-Ruvalcaba syndrome, hereditary diffuse gastric cancer, Peutz-Jeghers syndrome, Cowden syndrome, Neurofibromatosis type 1, or Fanconi anemia) are also recommended for annual screening MRI beginning between ages 20-35, depending on the mutation.¹⁴ Women with known pathogenic mutations in ATM, CHEK2, or NBN should consider annual MRI starting at age 40 or 5-10 years before the earliest known breast cancer in the family (whichever comes first). 

Finally, women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer,^4,15,16 with risk similar in magnitude to pathogenic BRCA1 or BRCA2  carriers. These women are also recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.

Currently the Tyrer-Cuzick Model (IBIS) version 817 and the Breast Cancer Surveillance Consortium (BCSC) models¹⁸ include breast density in risk calculations; the Gail, Penn II, and Claus models do not include breast density. 

Adding polygenic risk scores based on single nucleotide polymorphisms to traditional comprehensive risk models such as the Tyrer-Cuzick model has been shown to improve model performance.¹⁹ In addition, artificial intelligence is being used to identify textural and other findings beyond breast density on mammograms that predict increased risk. Such information, which is complementary to the Tyrer-Cuzick model (v.8),²⁰ has more accurately identified high-risk patients than the Tyrer-Cuzick v8 risk model and prior deep learning models.²¹ 

In a study from the Karolinska Institute, a model that included computer-aided detection of microcalcifications and masses in addition to other traditional risk factors (including breast density) successfully identified women who would develop interval or advanced cancer in the 2 years after a normal mammogram and improved short-term (2-to-3-year) risk assessment over TyrerCuzick (v.7) or Gail models.²² This model proved more accurate than traditional risk models and can augment genetic/family history to help identify women who should and, importantly, who should not, have supplemental screening after 2D mammography. Risk models that include detailed family history should be used rather than the Gail model to identify women who meet high risk criteria for MRI screening. Research also supports the benefits of MRI in women with dense breasts who are not otherwise considered “high risk,” and while not widely available, lower cost, abbreviated MRI protocols have been validated for all women with dense breasts.²³ For more details on risk models, including a risk models table with live links to commonly used breast cancer risk assessment tools, visit https://densebreast-info .org/for-providers/risk-model-tutorial/. ●

_{Text copyright DenseBreast-info.org.}

Answer

B.  The Gail risk model^1-3 is used to predict 5-year and lifetime risks of developing invasive breast cancer, and to identify women who may benefit from risk-reducing medications such as tamoxifen. The Gail model should not be used to determine risk for purposes of screening magnetic resonance imaging (MRI)⁴ (or genetic testing).

Breast cancer risk models are used to stratify patients into risk categories to facilitate personalized screening and surveillance plans for clinical management. Several breast cancer risk assessment tools have been developed that include different combinations of known risk factors and are used for the following purposes: 

1. To identify women who may benefit from risk-reducing medications. The Gail model is used to determine risk for purposes of advising on use of risk-reducing medications. Any woman with a 5-year risk ≥1.67% by the Gail model may be considered for treatment with tamoxifen (pre or postmenopausal), raloxifene (postmenopausal), or aromatase inhibitors (postmenopausal).⁵  

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 study,⁶ women at increased risk for breast cancer were defined as follows: 

• age 35 to 59 years with at least a 1.66% 5-year risk for developing breast cancer by the Gail model
• personal history of lobular carcinoma in situ (LCIS)
• age over 60 years.

More than 13,000 such women were randomly assigned to receive tamoxifen or placebo daily for 5 years. Tamoxifen reduced the risk of invasive breast cancer by 49% and reduced the risk of noninvasive cancer by 50% compared with placebo. The reduced risk of breast cancer was only seen for estrogen-receptor–expressing tumors. There was a 2.5-fold increase in risk of endometrial cancer in women taking tamoxifen and a decrease in hip and spine fracture risk. Blood clots causing stroke and deep vein thrombosis are increased in women taking tamoxifen.^7,8

2. To identify women who may carry a pathogenic mutation in BRCA1 or BRCA2. Some models (eg, Tyrer-Cuzick [IBIS],⁹ Penn II,¹⁰ BOADICEA,¹¹ and BRCAPRO¹²) estimate the probability of a BRCA1/2 mutation; however, most testing guidelines are now criterion based (eg, National Comprehensive Cancer Network [NCCN]) as opposed to probability based. In practical terms, clinical decision making around genetic testing is rarely based on a priori probabilities. 

3.  To identify women who meet criteria for high-risk screening MRI. Current American Cancer Society (ACS) guidelines⁴ recommend annual screening MRI, in addition to mammography, beginning by age 25 to 30 in women who have a lifetime risk of breast cancer ≥20%. Any of the models used to predict risk of a pathogenic mutation (Tyrer-Cuzick [IBIS], Penn II, BOADICEA, BRCAPRO),or the Claus model,¹³ but not the Gail model, can be used to estimate lifetime risk for purposes of screening MRI guidelines. The ACS and NCCN guidelines specifically recommend against using the Gail model to determine risk for purposes of MRI screening or risk of pathogenic mutation, as it does not include detailed family history such as age at diagnosis or second-degree relatives. 

ACS and NCCN guidelines also recommend annual screening MRI beginning by age 25, with the addition of mammography beginning at age 30, in women who are known to carry pathogenic mutations in BRCA1 or BRCA2 (unless the woman has had bilateral mastectomy), and in women who are first-degree relatives of known mutation carriers but who are themselves untested.¹⁴ 

Women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations (such as those associated with Li-Fraumeni syndrome, Bannayan-Riley-Ruvalcaba syndrome, hereditary diffuse gastric cancer, Peutz-Jeghers syndrome, Cowden syndrome, Neurofibromatosis type 1, or Fanconi anemia) are also recommended for annual screening MRI beginning between ages 20-35, depending on the mutation.¹⁴ Women with known pathogenic mutations in ATM, CHEK2, or NBN should consider annual MRI starting at age 40 or 5-10 years before the earliest known breast cancer in the family (whichever comes first). 

Finally, women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer,^4,15,16 with risk similar in magnitude to pathogenic BRCA1 or BRCA2  carriers. These women are also recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.

Currently the Tyrer-Cuzick Model (IBIS) version 817 and the Breast Cancer Surveillance Consortium (BCSC) models¹⁸ include breast density in risk calculations; the Gail, Penn II, and Claus models do not include breast density. 

Adding polygenic risk scores based on single nucleotide polymorphisms to traditional comprehensive risk models such as the Tyrer-Cuzick model has been shown to improve model performance.¹⁹ In addition, artificial intelligence is being used to identify textural and other findings beyond breast density on mammograms that predict increased risk. Such information, which is complementary to the Tyrer-Cuzick model (v.8),²⁰ has more accurately identified high-risk patients than the Tyrer-Cuzick v8 risk model and prior deep learning models.²¹ 

In a study from the Karolinska Institute, a model that included computer-aided detection of microcalcifications and masses in addition to other traditional risk factors (including breast density) successfully identified women who would develop interval or advanced cancer in the 2 years after a normal mammogram and improved short-term (2-to-3-year) risk assessment over TyrerCuzick (v.7) or Gail models.²² This model proved more accurate than traditional risk models and can augment genetic/family history to help identify women who should and, importantly, who should not, have supplemental screening after 2D mammography. Risk models that include detailed family history should be used rather than the Gail model to identify women who meet high risk criteria for MRI screening. Research also supports the benefits of MRI in women with dense breasts who are not otherwise considered “high risk,” and while not widely available, lower cost, abbreviated MRI protocols have been validated for all women with dense breasts.²³ For more details on risk models, including a risk models table with live links to commonly used breast cancer risk assessment tools, visit https://densebreast-info .org/for-providers/risk-model-tutorial/. ●

Sips of pickle juice may be all it takes to lessen the severity of muscle cramps in adults with cirrhosis, according to results of the PICCLES randomized controlled trial.

In the trial, patients with cirrhotic cramps who sipped pickle brine at the onset of a muscle cramp saw a significant decrease in cramp severity relative to peers who sipped tap water when the cramp hit.

“The acid (vinegar) in the brine triggers a nerve reflex to stop the cramp when it hits the throat. This is why only a sip is needed,” lead investigator Elliot Tapper, MD, division of gastroenterology and hepatology, University of Michigan, Ann Arbor, told this news organization. The study was published online April 13 in American Journal of Gastroenterology.
 

Common and bothersome

Cramps are common in adults with cirrhosis, irrespective of disease severity. They can sometimes last for hours, and treatment options are limited.

In a prior study, 1 tablespoon of pickle juice rapidly stopped experimentally induced cramps.

“This is something that athletes use, and kidney doctors often recommend to their patients, so it is nothing unique to cirrhosis,” Dr. Tapper said.

The PICCLES trial involved 74 adults (mean age, 56.6 years) with at least 4 muscle cramps in the prior month. In the cohort, 54% were men, and 41% had ascites.

The median cramp frequency was 11-12 per month, with an average cramp severity of more than 4 out of 10 on the Visual Analog Scale (VAS) for cramps. 

Some patients were receiving medications for their cramps at baseline, such as magnesium, potassium, baclofen, vitamin E, taurine, and gabapentin/pregabalin.

Thirty-eight patients were randomly allocated to sip pickle juice and 36 to sip tap water at the onset of a muscle cramp.

The proportion of cramps treated was similar in the pickle juice and tap water groups (77% and 72%). More patients in the pickle juice group said their cramps were aborted by the intervention (69% vs. 40%).

The primary outcome was the change in cramp severity at 28-days VAS for cramps. Cramps were assessed 10 times over 28 days using interactive text messages.

Pickle juice was associated with a larger average reduction in cramp severity than tap water (–2.25 points vs. –0.36 on the VAS-cramps), a difference that was statistically significant (P = .03).

There were no significant changes in the proportion of days with cramp severity of more than 5 on the VAS, or on sleep quality or health-related quality of life. 

Because pickle juice contains sodium, the researchers also assessed weight change as a safety outcome. They found no significant differences in weight change between the two groups overall or in the subset with ascites.

Pickle juice is a “safe option that can stop painful cramps,” Dr. Tapper said in an interview, but was “disheartened” that it did not improve quality of life.

Dr. Tapper encourages patients with cramps to ask their doctor about pickle juice and doctors to ask their patients about muscle cramps.

“Awareness of a patient’s cramps is often lacking. Asking about cramps is not routine but could be the most important advance relating to this study,” he said.

While sips of pickle juice are “unlikely to cause harm,” Dr. Tapper said, he is “a little nervous about advising patients to address their complex needs alone. [Doctors] are there to think through the root causes and help make adjustments that could prevent the cramps in the first place,” he said.
 

Outside experts weigh in

This news organization reached out to several outside experts for their perspective on the study.

Nancy Reau, MD, professor of internal medicine, associate director of solid organ transplantation, and section chief of hepatology. Rush University Medical Center, Chicago, noted that interventions to manage and prevent muscle cramps are “important, as cramping is common in cirrhosis and strongly affects quality of life.”

Dr. Reau cautioned that while pickle juice “sounds benign, it does have a lot of salt. Despite the salt content, this study didn’t show any difference between patients with and without ascites.

“However, cramping is more common in our patients with sarcopenia and those on diuretics for fluid management and it would be easy to see how this might impact fluid management,” Dr. Reau noted.

“Given that it is the acid (not the salt) in the pickle juice, there might be low salt alternatives,” Dr. Reau said.

Echoing Dr. Reau, Ankur Shah, MD, division of kidney disease and hypertension, Brown University, Providence, R.I., noted that “overuse of pickle juice could place patients at risk of developing high blood pressure and fluid overload, and pickle juice should be included in the sodium restriction guidance given to patients with high blood pressure and heart failure.”

In this study, however, the individual dose consumed was low, Dr. Shah noted.

He said the study “elegantly provides evidence to support the practice of sipping pickle juice for cramping.”

The authors should be “applauded for studying a simple solution with the most rigorous of methodologies, a randomized controlled trial,” Dr. Shah added.  

“This simple treatment may be helpful to patients far beyond those with just cirrhosis, and expect future studies to explore this treatment in other populations,” Dr. Shah said in an interview.

Paul Martin, MD, chief of the division of digestive health and liver diseases and Mandel Chair in Gastroenterology, University of Miami, noted that, while muscle cramps can have a major impact on quality of life, “in terms of some of the other complications of cirrhosis that health care providers are dealing with, they may seem relatively innocuous, but obviously patients have a slightly different interpretation because of the effect cramps can have on sleep and so on.

“There have been a variety of home remedies to treat muscle cramps, but this study is intriguing as it suggests that pickle juice, which is freely available, helps mitigate the severity of the cramps. However, it’s unclear whether it prevents cramps,” Dr. Martin said in an interview.

Given that the study is getting traction on Twitter, Dr. Martin encouraged health care providers to be aware of the study and prepared to answer questions from patients.

The study had no specific funding. Dr. Tapper has served as a consultant to Novartis, Axcella, and Allergan, has served on advisory boards for Mallinckrodt, Bausch Health, Kaleido, and Novo Nordisk, and has received unrestricted research grants from Gilead and Valeant. Dr. Reau, Dr. Shah, and Dr. Martin have disclosed no relevant financial relationships.

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

Sips of pickle juice may be all it takes to lessen the severity of muscle cramps in adults with cirrhosis, according to results of the PICCLES randomized controlled trial.

In the trial, patients with cirrhotic cramps who sipped pickle brine at the onset of a muscle cramp saw a significant decrease in cramp severity relative to peers who sipped tap water when the cramp hit.

“The acid (vinegar) in the brine triggers a nerve reflex to stop the cramp when it hits the throat. This is why only a sip is needed,” lead investigator Elliot Tapper, MD, division of gastroenterology and hepatology, University of Michigan, Ann Arbor, told this news organization. The study was published online April 13 in American Journal of Gastroenterology.
 

Common and bothersome

Cramps are common in adults with cirrhosis, irrespective of disease severity. They can sometimes last for hours, and treatment options are limited.

In a prior study, 1 tablespoon of pickle juice rapidly stopped experimentally induced cramps.

“This is something that athletes use, and kidney doctors often recommend to their patients, so it is nothing unique to cirrhosis,” Dr. Tapper said.

The PICCLES trial involved 74 adults (mean age, 56.6 years) with at least 4 muscle cramps in the prior month. In the cohort, 54% were men, and 41% had ascites.

The median cramp frequency was 11-12 per month, with an average cramp severity of more than 4 out of 10 on the Visual Analog Scale (VAS) for cramps. 

Some patients were receiving medications for their cramps at baseline, such as magnesium, potassium, baclofen, vitamin E, taurine, and gabapentin/pregabalin.

Thirty-eight patients were randomly allocated to sip pickle juice and 36 to sip tap water at the onset of a muscle cramp.

The proportion of cramps treated was similar in the pickle juice and tap water groups (77% and 72%). More patients in the pickle juice group said their cramps were aborted by the intervention (69% vs. 40%).

The primary outcome was the change in cramp severity at 28-days VAS for cramps. Cramps were assessed 10 times over 28 days using interactive text messages.

Pickle juice was associated with a larger average reduction in cramp severity than tap water (–2.25 points vs. –0.36 on the VAS-cramps), a difference that was statistically significant (P = .03).

There were no significant changes in the proportion of days with cramp severity of more than 5 on the VAS, or on sleep quality or health-related quality of life. 

Because pickle juice contains sodium, the researchers also assessed weight change as a safety outcome. They found no significant differences in weight change between the two groups overall or in the subset with ascites.

Pickle juice is a “safe option that can stop painful cramps,” Dr. Tapper said in an interview, but was “disheartened” that it did not improve quality of life.

Dr. Tapper encourages patients with cramps to ask their doctor about pickle juice and doctors to ask their patients about muscle cramps.

“Awareness of a patient’s cramps is often lacking. Asking about cramps is not routine but could be the most important advance relating to this study,” he said.

While sips of pickle juice are “unlikely to cause harm,” Dr. Tapper said, he is “a little nervous about advising patients to address their complex needs alone. [Doctors] are there to think through the root causes and help make adjustments that could prevent the cramps in the first place,” he said.
 

Outside experts weigh in

This news organization reached out to several outside experts for their perspective on the study.

Nancy Reau, MD, professor of internal medicine, associate director of solid organ transplantation, and section chief of hepatology. Rush University Medical Center, Chicago, noted that interventions to manage and prevent muscle cramps are “important, as cramping is common in cirrhosis and strongly affects quality of life.”

Dr. Reau cautioned that while pickle juice “sounds benign, it does have a lot of salt. Despite the salt content, this study didn’t show any difference between patients with and without ascites.

“However, cramping is more common in our patients with sarcopenia and those on diuretics for fluid management and it would be easy to see how this might impact fluid management,” Dr. Reau noted.

“Given that it is the acid (not the salt) in the pickle juice, there might be low salt alternatives,” Dr. Reau said.

Echoing Dr. Reau, Ankur Shah, MD, division of kidney disease and hypertension, Brown University, Providence, R.I., noted that “overuse of pickle juice could place patients at risk of developing high blood pressure and fluid overload, and pickle juice should be included in the sodium restriction guidance given to patients with high blood pressure and heart failure.”

In this study, however, the individual dose consumed was low, Dr. Shah noted.

He said the study “elegantly provides evidence to support the practice of sipping pickle juice for cramping.”

The authors should be “applauded for studying a simple solution with the most rigorous of methodologies, a randomized controlled trial,” Dr. Shah added.  

“This simple treatment may be helpful to patients far beyond those with just cirrhosis, and expect future studies to explore this treatment in other populations,” Dr. Shah said in an interview.

Paul Martin, MD, chief of the division of digestive health and liver diseases and Mandel Chair in Gastroenterology, University of Miami, noted that, while muscle cramps can have a major impact on quality of life, “in terms of some of the other complications of cirrhosis that health care providers are dealing with, they may seem relatively innocuous, but obviously patients have a slightly different interpretation because of the effect cramps can have on sleep and so on.

“There have been a variety of home remedies to treat muscle cramps, but this study is intriguing as it suggests that pickle juice, which is freely available, helps mitigate the severity of the cramps. However, it’s unclear whether it prevents cramps,” Dr. Martin said in an interview.

Given that the study is getting traction on Twitter, Dr. Martin encouraged health care providers to be aware of the study and prepared to answer questions from patients.

The study had no specific funding. Dr. Tapper has served as a consultant to Novartis, Axcella, and Allergan, has served on advisory boards for Mallinckrodt, Bausch Health, Kaleido, and Novo Nordisk, and has received unrestricted research grants from Gilead and Valeant. Dr. Reau, Dr. Shah, and Dr. Martin have disclosed no relevant financial relationships.

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

Sips of pickle juice may be all it takes to lessen the severity of muscle cramps in adults with cirrhosis, according to results of the PICCLES randomized controlled trial.

In the trial, patients with cirrhotic cramps who sipped pickle brine at the onset of a muscle cramp saw a significant decrease in cramp severity relative to peers who sipped tap water when the cramp hit.

“The acid (vinegar) in the brine triggers a nerve reflex to stop the cramp when it hits the throat. This is why only a sip is needed,” lead investigator Elliot Tapper, MD, division of gastroenterology and hepatology, University of Michigan, Ann Arbor, told this news organization. The study was published online April 13 in American Journal of Gastroenterology.
 

Common and bothersome

Cramps are common in adults with cirrhosis, irrespective of disease severity. They can sometimes last for hours, and treatment options are limited.

In a prior study, 1 tablespoon of pickle juice rapidly stopped experimentally induced cramps.

“This is something that athletes use, and kidney doctors often recommend to their patients, so it is nothing unique to cirrhosis,” Dr. Tapper said.

The PICCLES trial involved 74 adults (mean age, 56.6 years) with at least 4 muscle cramps in the prior month. In the cohort, 54% were men, and 41% had ascites.

The median cramp frequency was 11-12 per month, with an average cramp severity of more than 4 out of 10 on the Visual Analog Scale (VAS) for cramps. 

Some patients were receiving medications for their cramps at baseline, such as magnesium, potassium, baclofen, vitamin E, taurine, and gabapentin/pregabalin.

Thirty-eight patients were randomly allocated to sip pickle juice and 36 to sip tap water at the onset of a muscle cramp.

The proportion of cramps treated was similar in the pickle juice and tap water groups (77% and 72%). More patients in the pickle juice group said their cramps were aborted by the intervention (69% vs. 40%).

The primary outcome was the change in cramp severity at 28-days VAS for cramps. Cramps were assessed 10 times over 28 days using interactive text messages.

Pickle juice was associated with a larger average reduction in cramp severity than tap water (–2.25 points vs. –0.36 on the VAS-cramps), a difference that was statistically significant (P = .03).

There were no significant changes in the proportion of days with cramp severity of more than 5 on the VAS, or on sleep quality or health-related quality of life. 

Because pickle juice contains sodium, the researchers also assessed weight change as a safety outcome. They found no significant differences in weight change between the two groups overall or in the subset with ascites.

Pickle juice is a “safe option that can stop painful cramps,” Dr. Tapper said in an interview, but was “disheartened” that it did not improve quality of life.

Dr. Tapper encourages patients with cramps to ask their doctor about pickle juice and doctors to ask their patients about muscle cramps.

“Awareness of a patient’s cramps is often lacking. Asking about cramps is not routine but could be the most important advance relating to this study,” he said.

While sips of pickle juice are “unlikely to cause harm,” Dr. Tapper said, he is “a little nervous about advising patients to address their complex needs alone. [Doctors] are there to think through the root causes and help make adjustments that could prevent the cramps in the first place,” he said.
 

Outside experts weigh in

This news organization reached out to several outside experts for their perspective on the study.

Nancy Reau, MD, professor of internal medicine, associate director of solid organ transplantation, and section chief of hepatology. Rush University Medical Center, Chicago, noted that interventions to manage and prevent muscle cramps are “important, as cramping is common in cirrhosis and strongly affects quality of life.”

Dr. Reau cautioned that while pickle juice “sounds benign, it does have a lot of salt. Despite the salt content, this study didn’t show any difference between patients with and without ascites.

“However, cramping is more common in our patients with sarcopenia and those on diuretics for fluid management and it would be easy to see how this might impact fluid management,” Dr. Reau noted.

“Given that it is the acid (not the salt) in the pickle juice, there might be low salt alternatives,” Dr. Reau said.

Echoing Dr. Reau, Ankur Shah, MD, division of kidney disease and hypertension, Brown University, Providence, R.I., noted that “overuse of pickle juice could place patients at risk of developing high blood pressure and fluid overload, and pickle juice should be included in the sodium restriction guidance given to patients with high blood pressure and heart failure.”

In this study, however, the individual dose consumed was low, Dr. Shah noted.

He said the study “elegantly provides evidence to support the practice of sipping pickle juice for cramping.”

The authors should be “applauded for studying a simple solution with the most rigorous of methodologies, a randomized controlled trial,” Dr. Shah added.  

“This simple treatment may be helpful to patients far beyond those with just cirrhosis, and expect future studies to explore this treatment in other populations,” Dr. Shah said in an interview.

Paul Martin, MD, chief of the division of digestive health and liver diseases and Mandel Chair in Gastroenterology, University of Miami, noted that, while muscle cramps can have a major impact on quality of life, “in terms of some of the other complications of cirrhosis that health care providers are dealing with, they may seem relatively innocuous, but obviously patients have a slightly different interpretation because of the effect cramps can have on sleep and so on.

“There have been a variety of home remedies to treat muscle cramps, but this study is intriguing as it suggests that pickle juice, which is freely available, helps mitigate the severity of the cramps. However, it’s unclear whether it prevents cramps,” Dr. Martin said in an interview.

Given that the study is getting traction on Twitter, Dr. Martin encouraged health care providers to be aware of the study and prepared to answer questions from patients.

The study had no specific funding. Dr. Tapper has served as a consultant to Novartis, Axcella, and Allergan, has served on advisory boards for Mallinckrodt, Bausch Health, Kaleido, and Novo Nordisk, and has received unrestricted research grants from Gilead and Valeant. Dr. Reau, Dr. Shah, and Dr. Martin have disclosed no relevant financial relationships.

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

Difficult economic times and the unpredictable consequences of health care reform are making an increasing number of solo practitioners and small private groups very nervous. Yet, many balk at the prospect of selling to private equity companies. I have received many inquiries about other protective options, such as merging two or more small practices into one larger entity.

Merging offers many benefits: Better overall management, centralized and efficient billing and collection, group purchasing discounts, and reduced overhead, among others; but careful planning, and a written agreement, are essential. If you are considering such an option, here are some things to think about.

You should begin with an evaluation and comparison of the separate groups’ respective finances. This should include a history of production, collections, overhead, and liabilities. Basically, you want to locate and identify all assets and liabilities that will be combined into the new group. One area of immediate importance is Medicare participation. Which members now currently participate and which do not? Since the new group will need to have a single position, all of the physicians must agree on that issue.

Who will be in charge? Not every physician is a qualified manager. The manager should be the physician who is willing to spend the time it takes to sign checks, interact with the administrator, and ensure that other matters such as filing tax returns and approving minor purchases arc carried out properly.

What is the compensation formula? Compensation arrangements should be based on each physician’s current financial data and the goals of the practice. Will everyone be paid only for what they do individually, or will revenue be shared equally? I favor a combination, so productivity is rewarded but your income doesn’t drop to zero when you take time off.

Which practices have a retirement plan and which do not? Will you keep your retirement plans separate, or combine them? If the latter, you will have to agree on the terms of the new plan, which can be the same or different from any of the existing plans. You’ll probably need some legal guidance to insure that assets from existing plans can be transferred into a new plan without tax issues. You may also have to address the problem of physicians who currently do not have a plan who, for whatever reason, may not want to be forced into making retirement plan contributions.

The often-problematic issue of employees and their salaries needs to be addressed, to decide which employees will be needed in the new group, and to determine a salary structure. Each practice’s policies related to vacation, sick leave, and other such issues should be reviewed, and an overall policy for the new group developed.

Other common sticking points are issues related to facilities. If the practices intend to consolidate into one location, the physicians must decide which of the specific assets of each practice will be contributed to the new entity. Ideally, each party brings an equal amount of assets to the table, but in the real world that is hardly ever the case. Physicians whose assets are to be used generally want to be compensated, and those who have to dispose of or store assets are in a quandary. The solution to this predicament will vary depending on the circumstances of each merger. One alternative is to agree that any inequalities will be compensated at the other end, in the form of buyout value; that is, physicians contributing more assets will receive larger buyouts when they leave or retire than those contributing less.

Buyouts should be addressed in advance as well. You must decide when a buyout would occur – usually in the event of retirement, death, disability, or withdrawal (voluntary or involuntary) – how the buyout amount will be calculated, and how it will be paid. Then, you must agree on how a buyout amount will be valued. Remember that any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. I suggest having an actuary create a formula, so that the buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

Noncompete provisions are always a difficult issue, mostly because they are so hard (and expensive) to enforce. An increasingly popular alternative is, once again, to deal with it at the other end, with a buyout penalty. An unhappy partner can leave, and compete, but at the cost of a substantially reduced buyout. This permits competition, but discourages it; and it compensates the remaining partners.

These are only some of the pivotal business and legal issues that must be settled in advance. A little planning and negotiation can prevent a lot of grief, regret, and legal expenses in the future. I’ll discuss some other, more complicated merger options in my next column.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Difficult economic times and the unpredictable consequences of health care reform are making an increasing number of solo practitioners and small private groups very nervous. Yet, many balk at the prospect of selling to private equity companies. I have received many inquiries about other protective options, such as merging two or more small practices into one larger entity.

Merging offers many benefits: Better overall management, centralized and efficient billing and collection, group purchasing discounts, and reduced overhead, among others; but careful planning, and a written agreement, are essential. If you are considering such an option, here are some things to think about.

You should begin with an evaluation and comparison of the separate groups’ respective finances. This should include a history of production, collections, overhead, and liabilities. Basically, you want to locate and identify all assets and liabilities that will be combined into the new group. One area of immediate importance is Medicare participation. Which members now currently participate and which do not? Since the new group will need to have a single position, all of the physicians must agree on that issue.

Who will be in charge? Not every physician is a qualified manager. The manager should be the physician who is willing to spend the time it takes to sign checks, interact with the administrator, and ensure that other matters such as filing tax returns and approving minor purchases arc carried out properly.

What is the compensation formula? Compensation arrangements should be based on each physician’s current financial data and the goals of the practice. Will everyone be paid only for what they do individually, or will revenue be shared equally? I favor a combination, so productivity is rewarded but your income doesn’t drop to zero when you take time off.

Which practices have a retirement plan and which do not? Will you keep your retirement plans separate, or combine them? If the latter, you will have to agree on the terms of the new plan, which can be the same or different from any of the existing plans. You’ll probably need some legal guidance to insure that assets from existing plans can be transferred into a new plan without tax issues. You may also have to address the problem of physicians who currently do not have a plan who, for whatever reason, may not want to be forced into making retirement plan contributions.

The often-problematic issue of employees and their salaries needs to be addressed, to decide which employees will be needed in the new group, and to determine a salary structure. Each practice’s policies related to vacation, sick leave, and other such issues should be reviewed, and an overall policy for the new group developed.

Other common sticking points are issues related to facilities. If the practices intend to consolidate into one location, the physicians must decide which of the specific assets of each practice will be contributed to the new entity. Ideally, each party brings an equal amount of assets to the table, but in the real world that is hardly ever the case. Physicians whose assets are to be used generally want to be compensated, and those who have to dispose of or store assets are in a quandary. The solution to this predicament will vary depending on the circumstances of each merger. One alternative is to agree that any inequalities will be compensated at the other end, in the form of buyout value; that is, physicians contributing more assets will receive larger buyouts when they leave or retire than those contributing less.

Buyouts should be addressed in advance as well. You must decide when a buyout would occur – usually in the event of retirement, death, disability, or withdrawal (voluntary or involuntary) – how the buyout amount will be calculated, and how it will be paid. Then, you must agree on how a buyout amount will be valued. Remember that any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. I suggest having an actuary create a formula, so that the buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

Noncompete provisions are always a difficult issue, mostly because they are so hard (and expensive) to enforce. An increasingly popular alternative is, once again, to deal with it at the other end, with a buyout penalty. An unhappy partner can leave, and compete, but at the cost of a substantially reduced buyout. This permits competition, but discourages it; and it compensates the remaining partners.

These are only some of the pivotal business and legal issues that must be settled in advance. A little planning and negotiation can prevent a lot of grief, regret, and legal expenses in the future. I’ll discuss some other, more complicated merger options in my next column.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Difficult economic times and the unpredictable consequences of health care reform are making an increasing number of solo practitioners and small private groups very nervous. Yet, many balk at the prospect of selling to private equity companies. I have received many inquiries about other protective options, such as merging two or more small practices into one larger entity.

Merging offers many benefits: Better overall management, centralized and efficient billing and collection, group purchasing discounts, and reduced overhead, among others; but careful planning, and a written agreement, are essential. If you are considering such an option, here are some things to think about.

You should begin with an evaluation and comparison of the separate groups’ respective finances. This should include a history of production, collections, overhead, and liabilities. Basically, you want to locate and identify all assets and liabilities that will be combined into the new group. One area of immediate importance is Medicare participation. Which members now currently participate and which do not? Since the new group will need to have a single position, all of the physicians must agree on that issue.

Who will be in charge? Not every physician is a qualified manager. The manager should be the physician who is willing to spend the time it takes to sign checks, interact with the administrator, and ensure that other matters such as filing tax returns and approving minor purchases arc carried out properly.

What is the compensation formula? Compensation arrangements should be based on each physician’s current financial data and the goals of the practice. Will everyone be paid only for what they do individually, or will revenue be shared equally? I favor a combination, so productivity is rewarded but your income doesn’t drop to zero when you take time off.

Which practices have a retirement plan and which do not? Will you keep your retirement plans separate, or combine them? If the latter, you will have to agree on the terms of the new plan, which can be the same or different from any of the existing plans. You’ll probably need some legal guidance to insure that assets from existing plans can be transferred into a new plan without tax issues. You may also have to address the problem of physicians who currently do not have a plan who, for whatever reason, may not want to be forced into making retirement plan contributions.

The often-problematic issue of employees and their salaries needs to be addressed, to decide which employees will be needed in the new group, and to determine a salary structure. Each practice’s policies related to vacation, sick leave, and other such issues should be reviewed, and an overall policy for the new group developed.

Other common sticking points are issues related to facilities. If the practices intend to consolidate into one location, the physicians must decide which of the specific assets of each practice will be contributed to the new entity. Ideally, each party brings an equal amount of assets to the table, but in the real world that is hardly ever the case. Physicians whose assets are to be used generally want to be compensated, and those who have to dispose of or store assets are in a quandary. The solution to this predicament will vary depending on the circumstances of each merger. One alternative is to agree that any inequalities will be compensated at the other end, in the form of buyout value; that is, physicians contributing more assets will receive larger buyouts when they leave or retire than those contributing less.

Buyouts should be addressed in advance as well. You must decide when a buyout would occur – usually in the event of retirement, death, disability, or withdrawal (voluntary or involuntary) – how the buyout amount will be calculated, and how it will be paid. Then, you must agree on how a buyout amount will be valued. Remember that any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. I suggest having an actuary create a formula, so that the buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

Noncompete provisions are always a difficult issue, mostly because they are so hard (and expensive) to enforce. An increasingly popular alternative is, once again, to deal with it at the other end, with a buyout penalty. An unhappy partner can leave, and compete, but at the cost of a substantially reduced buyout. This permits competition, but discourages it; and it compensates the remaining partners.

These are only some of the pivotal business and legal issues that must be settled in advance. A little planning and negotiation can prevent a lot of grief, regret, and legal expenses in the future. I’ll discuss some other, more complicated merger options in my next column.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

During the first year of the pandemic, at least four people in Michigan were infected with a coronavirus variant that has been found in mink.

The cluster, which previously included three cases, marks the first known instance of likely animal-to-human “spillover” of the virus in the United States, according to the New York Times. All four people fully recovered.

Two of the infected people were employees of a mink farm in Michigan that had an outbreak in October 2020. The other two people didn’t have known links to the farm, which may mean that the coronavirus variant among mink may have been circulating more widely among residents in that area during that time.

Virus samples from all four people contained two mutations that may show signs of an adaptation to mink. The mutations have also been documented in farmed mink in Europe and people with connections to those farms.

“This, in addition to the mink farmworkers testing positive for COVID-19 after the mink herd had begun experiencing illness and increased mortality, suggests that the most likely hypothesis is that the workers were infected after contact with mink on the farm,” Casey Barton Behravesh, DVM, who directs the Centers for Disease Control and Prevention’s One Health Office, told the newspaper.

But researchers are unable to prove the cause, she noted.

“Because there are few genetic sequences available from the communities around the farm, it is impossible to know for sure whether the mutations came from mink on the farm or were already circulating in the community,” she said.

In August 2020, the U.S. Department of Agriculture announced the first confirmed COVID-19 case in mink at farms in Utah, followed by a case in Wisconsin. Worldwide, the coronavirus has been detected in mink on farms in the Netherlands, Denmark, Poland, and Spain.

In early October 2020, Michigan officials announced that the coronavirus had been detected in mink on a local farm. Several of the animals had died. The CDC helped to investigate the outbreak by collecting samples from animals, farmworkers, and residents in the community.

By March 2021, the CDC had updated its website to note that a “small number of people” had contracted a coronavirus variant that “contained unique mink-related mutations.”

In April 2021, the Detroit Free Press and the Documenting COVID-19 project first reported on the first three cases – two farmworkers and a taxidermist who didn’t have a connection to the mink farm. This week, the news outlets reported an update that the fourth case was the taxidermist’s wife.

Earlier this month, National Geographic first reported on the fourth human case based on government documents about the mink farm outbreak.

Overall, animal-to-human transmission is rare, but the CDC is continuing to monitor potential coronavirus cases in wildlife, livestock, and zoo animals for new variants and virus reservoirs, the Times reported.

“These results highlight the importance of routinely studying the genetic material of SARS-CoV-2 in susceptible animal populations like mink, as well as in people,” the CDC wrote.

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

During the first year of the pandemic, at least four people in Michigan were infected with a coronavirus variant that has been found in mink.

The cluster, which previously included three cases, marks the first known instance of likely animal-to-human “spillover” of the virus in the United States, according to the New York Times. All four people fully recovered.

Two of the infected people were employees of a mink farm in Michigan that had an outbreak in October 2020. The other two people didn’t have known links to the farm, which may mean that the coronavirus variant among mink may have been circulating more widely among residents in that area during that time.

Virus samples from all four people contained two mutations that may show signs of an adaptation to mink. The mutations have also been documented in farmed mink in Europe and people with connections to those farms.

“This, in addition to the mink farmworkers testing positive for COVID-19 after the mink herd had begun experiencing illness and increased mortality, suggests that the most likely hypothesis is that the workers were infected after contact with mink on the farm,” Casey Barton Behravesh, DVM, who directs the Centers for Disease Control and Prevention’s One Health Office, told the newspaper.

But researchers are unable to prove the cause, she noted.

“Because there are few genetic sequences available from the communities around the farm, it is impossible to know for sure whether the mutations came from mink on the farm or were already circulating in the community,” she said.

In August 2020, the U.S. Department of Agriculture announced the first confirmed COVID-19 case in mink at farms in Utah, followed by a case in Wisconsin. Worldwide, the coronavirus has been detected in mink on farms in the Netherlands, Denmark, Poland, and Spain.

In early October 2020, Michigan officials announced that the coronavirus had been detected in mink on a local farm. Several of the animals had died. The CDC helped to investigate the outbreak by collecting samples from animals, farmworkers, and residents in the community.

By March 2021, the CDC had updated its website to note that a “small number of people” had contracted a coronavirus variant that “contained unique mink-related mutations.”

In April 2021, the Detroit Free Press and the Documenting COVID-19 project first reported on the first three cases – two farmworkers and a taxidermist who didn’t have a connection to the mink farm. This week, the news outlets reported an update that the fourth case was the taxidermist’s wife.

Earlier this month, National Geographic first reported on the fourth human case based on government documents about the mink farm outbreak.

Overall, animal-to-human transmission is rare, but the CDC is continuing to monitor potential coronavirus cases in wildlife, livestock, and zoo animals for new variants and virus reservoirs, the Times reported.

“These results highlight the importance of routinely studying the genetic material of SARS-CoV-2 in susceptible animal populations like mink, as well as in people,” the CDC wrote.

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

During the first year of the pandemic, at least four people in Michigan were infected with a coronavirus variant that has been found in mink.

The cluster, which previously included three cases, marks the first known instance of likely animal-to-human “spillover” of the virus in the United States, according to the New York Times. All four people fully recovered.

Two of the infected people were employees of a mink farm in Michigan that had an outbreak in October 2020. The other two people didn’t have known links to the farm, which may mean that the coronavirus variant among mink may have been circulating more widely among residents in that area during that time.

Virus samples from all four people contained two mutations that may show signs of an adaptation to mink. The mutations have also been documented in farmed mink in Europe and people with connections to those farms.

“This, in addition to the mink farmworkers testing positive for COVID-19 after the mink herd had begun experiencing illness and increased mortality, suggests that the most likely hypothesis is that the workers were infected after contact with mink on the farm,” Casey Barton Behravesh, DVM, who directs the Centers for Disease Control and Prevention’s One Health Office, told the newspaper.

But researchers are unable to prove the cause, she noted.

“Because there are few genetic sequences available from the communities around the farm, it is impossible to know for sure whether the mutations came from mink on the farm or were already circulating in the community,” she said.

In August 2020, the U.S. Department of Agriculture announced the first confirmed COVID-19 case in mink at farms in Utah, followed by a case in Wisconsin. Worldwide, the coronavirus has been detected in mink on farms in the Netherlands, Denmark, Poland, and Spain.

In early October 2020, Michigan officials announced that the coronavirus had been detected in mink on a local farm. Several of the animals had died. The CDC helped to investigate the outbreak by collecting samples from animals, farmworkers, and residents in the community.

By March 2021, the CDC had updated its website to note that a “small number of people” had contracted a coronavirus variant that “contained unique mink-related mutations.”

In April 2021, the Detroit Free Press and the Documenting COVID-19 project first reported on the first three cases – two farmworkers and a taxidermist who didn’t have a connection to the mink farm. This week, the news outlets reported an update that the fourth case was the taxidermist’s wife.

Earlier this month, National Geographic first reported on the fourth human case based on government documents about the mink farm outbreak.

Overall, animal-to-human transmission is rare, but the CDC is continuing to monitor potential coronavirus cases in wildlife, livestock, and zoo animals for new variants and virus reservoirs, the Times reported.

“These results highlight the importance of routinely studying the genetic material of SARS-CoV-2 in susceptible animal populations like mink, as well as in people,” the CDC wrote.

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

It was a good run while it lasted.

New COVID-19 cases in U.S. children had dropped for 11 consecutive weeks, but that streak has come to an end, as cases increased 28% during the week of April 8-14, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The number of reported pediatric cases for the week was 33,146, and the actual increase from the previous week was just 7,231 cases, the AAP and CHA said, but some reports suggest that the new COVID variants and subvariants are starting to have an effect on incidence in some areas while mask mandates continue to fall.

Data from the Centers for Disease Control and Prevention show that, over the last week or two, the 7-day average for percentage of emergency department visits with diagnosed COVID has risen from 0.5% to 0.6% in children aged 0-11 years, from 0.3% to 0.5% among 12- to 15-year-olds, and from 0.3% to 0.4% in 16- and 17-year-olds. Small increases, to be sure, but increases nonetheless.

A somewhat similar scenario is playing out for new admissions of children aged 0-17, which have leveled out after dropping from a high of 1.25 per 100,000 population in mid-January to 0.13 per 100,000 in early April. Over the last 2 weeks, the rate has been alternating between 0.13 and 0.14 per 100,000, the CDC said on its COVID Data Tracker.

The latest news on the vaccination front came from Pfizer and BIoNTech, which announced that a third dose of its COVID-19 vaccine boosted immune protection in children aged 5-11 years in a phase 2/3 trial. Protection against the Omicron strain was 36 times higher than the two previous doses, the companies said, adding that they plan to submit a request for emergency use authorization of a booster dose in the near future.

The ongoing vaccination effort, however, produced mixed results in the last week. Initial vaccinations among children aged 5-11 years fell 14.5% to another new low while initial doses were up 9.3% for those aged 12-17, the AAP said. Overall, just 28.2% of the country’s 5- to 11-year-olds are fully vaccinated, compared with 58.7% of those aged 12-17, the CDC reported.

[email protected]

It was a good run while it lasted.

New COVID-19 cases in U.S. children had dropped for 11 consecutive weeks, but that streak has come to an end, as cases increased 28% during the week of April 8-14, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The number of reported pediatric cases for the week was 33,146, and the actual increase from the previous week was just 7,231 cases, the AAP and CHA said, but some reports suggest that the new COVID variants and subvariants are starting to have an effect on incidence in some areas while mask mandates continue to fall.

Data from the Centers for Disease Control and Prevention show that, over the last week or two, the 7-day average for percentage of emergency department visits with diagnosed COVID has risen from 0.5% to 0.6% in children aged 0-11 years, from 0.3% to 0.5% among 12- to 15-year-olds, and from 0.3% to 0.4% in 16- and 17-year-olds. Small increases, to be sure, but increases nonetheless.

A somewhat similar scenario is playing out for new admissions of children aged 0-17, which have leveled out after dropping from a high of 1.25 per 100,000 population in mid-January to 0.13 per 100,000 in early April. Over the last 2 weeks, the rate has been alternating between 0.13 and 0.14 per 100,000, the CDC said on its COVID Data Tracker.

The latest news on the vaccination front came from Pfizer and BIoNTech, which announced that a third dose of its COVID-19 vaccine boosted immune protection in children aged 5-11 years in a phase 2/3 trial. Protection against the Omicron strain was 36 times higher than the two previous doses, the companies said, adding that they plan to submit a request for emergency use authorization of a booster dose in the near future.

The ongoing vaccination effort, however, produced mixed results in the last week. Initial vaccinations among children aged 5-11 years fell 14.5% to another new low while initial doses were up 9.3% for those aged 12-17, the AAP said. Overall, just 28.2% of the country’s 5- to 11-year-olds are fully vaccinated, compared with 58.7% of those aged 12-17, the CDC reported.

[email protected]

It was a good run while it lasted.

New COVID-19 cases in U.S. children had dropped for 11 consecutive weeks, but that streak has come to an end, as cases increased 28% during the week of April 8-14, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The number of reported pediatric cases for the week was 33,146, and the actual increase from the previous week was just 7,231 cases, the AAP and CHA said, but some reports suggest that the new COVID variants and subvariants are starting to have an effect on incidence in some areas while mask mandates continue to fall.

Data from the Centers for Disease Control and Prevention show that, over the last week or two, the 7-day average for percentage of emergency department visits with diagnosed COVID has risen from 0.5% to 0.6% in children aged 0-11 years, from 0.3% to 0.5% among 12- to 15-year-olds, and from 0.3% to 0.4% in 16- and 17-year-olds. Small increases, to be sure, but increases nonetheless.

A somewhat similar scenario is playing out for new admissions of children aged 0-17, which have leveled out after dropping from a high of 1.25 per 100,000 population in mid-January to 0.13 per 100,000 in early April. Over the last 2 weeks, the rate has been alternating between 0.13 and 0.14 per 100,000, the CDC said on its COVID Data Tracker.

The latest news on the vaccination front came from Pfizer and BIoNTech, which announced that a third dose of its COVID-19 vaccine boosted immune protection in children aged 5-11 years in a phase 2/3 trial. Protection against the Omicron strain was 36 times higher than the two previous doses, the companies said, adding that they plan to submit a request for emergency use authorization of a booster dose in the near future.

The ongoing vaccination effort, however, produced mixed results in the last week. Initial vaccinations among children aged 5-11 years fell 14.5% to another new low while initial doses were up 9.3% for those aged 12-17, the AAP said. Overall, just 28.2% of the country’s 5- to 11-year-olds are fully vaccinated, compared with 58.7% of those aged 12-17, the CDC reported.

[email protected]

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

During her final years practicing medicine, the internist Faith Thayer Fitzgerald, MD, glided from room to room on a razor scooter at UC Davis Medical Center in Sacramento, Calif, her colleague recalled.

Dr. Fitzgerald adopted this means of transportation to allow her to examine and talk to her patients, following a hip injury and surgery, which left her unable to do the amount of walking typically required to conduct rounds at a hospital.

Courtesy UC Davis Health

Her colleague, Mark C. Henderson, MD, MACP, described Dr. Fitzgerald as being “extremely dedicated to each patient,” having taken care of many of them for decades. Her will to find a way to practice with severe physical limitations exemplified this dedication, said Dr. Henderson, who worked in the hospital alongside her, including handing over patients to her.

Dr. Fitzgerald died on Dec. 3, 2021, at 78 years, after working in a career spanning 6 decades, including actively practicing internal medicine at UC Davis Medical Center for 40 years.

Her career also included working as a medical educator, influencing several people interviewed for this story in that role, and advising the staff of Internal Medicine News for more than 3 decades.

“Faith Fitzgerald was an incredible teacher and mentor for so many people,” noted Robert H. Hopkins Jr., MD, who practices general internal medicine and med-peds at the University of Arkansans for Medical Sciences, Little Rock and is a member of the editorial advisory board of Internal Medicine News.
 

‘The patient and the next generation’ were always in mind

A contributor to Dr. Fitzgerald’s success as an educator was her dogged commitment to her patients, said Dr. Henderson, who is associate dean for admissions at the University of California, Davis, and professor and vice chair for education in the department of internal medicine. The latter of these positions was previously held by Dr. Fitzgerald.

“She always arrived early for hospital rounds, often waking up her patients,” he said. “She evolved this practice to be present before all the chaos of the day ensued and honestly to spend quality of time with patients.”

“She always had two things in mind: the patient and the next generation,” Dr. Henderson continued. “A lot of times, because she had seen the patients earlier in the morning, she knew where to focus the team she was training” and “she could show her students and residents all of these interesting findings.”

“It was a very efficient way of conducting bedside teaching,” he added.

Dr. Fitzgerald taught primarily in the department of internal medicine at UC Davis Health. She joined the faculty of that school in 1980. Her 38-year-long career there included serving as residency program director for nearly 20 years, chief of general medicine, vice chair for education, and the medical school’s first associate dean for humanities and bioethics.

Several people who knew Dr. Fitzgerald well also attributed her effectiveness as a teacher and a doctor to the kindness she showed all people no matter their background or station in life.

“Every patient she saw in clinic, she booked for an hour ‘til the day she left UC Davis,” noted Carmelina Raffetto, Dr. Fitzgerald’s closest friend and former administrative assistant, during UC Davis Health’s virtual memorial ceremony for Dr. Fitzgerald.

“Her patients all had her phone number, her pager. ... She loved teaching, she loved her patients, and she loved staff.

“She treated all of us equally. Whether you were in housekeeping or in the cafeteria, or if you were just walking down the hall, she had kind words and she never wanted anyone to feel that they weren’t’ special,” added Ms. Raffetto, who is currently executive director of the Northern California American College of Physicians chapter.

Throughout her career, she received over three dozen teaching awards, according to a statement from UC Davis. In 2002, for example, Dr. Fitzgerald received the Alpha Omega Alpha medical honor society’s Robert J. Glaser Award for providing medical students with an outstanding educational experience. Additional teaching awards included the American College of Physicians Distinguished Teacher Award, the California Medical Association Golden Apple Award and the UC San Francisco Gold Headed Cane.

She also received awards from UC Davis, including the Hibbard Williams Lifetime Achievement award, the Tupper Award for Excellence in Teaching and the UC Davis School of Medicine Golden Apple Award. She was also chosen as the UC Davis Senior Class Outstanding Clinical Teacher seven times and was named the Department of Medicine Distinguished Faculty Teacher on four separate occasions, the statement said.
 

Her early life and family

Dr. Fitzgerald was born in Boston on Sept. 24, 1943, and “knew from early childhood that she would be a physician,” according to her biography on Changing the Face of Medicine.

She completed undergraduate studies at the University of California, Santa Barbara. She graduated from the University of California, San Francisco, in 1969 and completed her residency in internal medicine at the same institution. In addition to teaching at UC Davis, Dr. Fitzgerald served as assistant professor of medicine at University of Michigan, Ann Arbor, for 2 years early in her career.

Dr. Fitzgerald is survived by her brother, Sean, and sister-in-law, Deborah Fitzgerald. Dr. Fitzgerald lived with and cared for her mother, Irene Fitzgerald – who passed away in 2005 – for more than a decade.

Dr. Fitzgerald asked for any donations in her memory to be used to establish scholarships for medical students with financial need, as she had been supported by scholarship money long ago while a student at the University of California. Donations to the Faith Fitzgerald, MD, Medical Student Scholarship Fund can be made here.

During her final years practicing medicine, the internist Faith Thayer Fitzgerald, MD, glided from room to room on a razor scooter at UC Davis Medical Center in Sacramento, Calif, her colleague recalled.

Dr. Fitzgerald adopted this means of transportation to allow her to examine and talk to her patients, following a hip injury and surgery, which left her unable to do the amount of walking typically required to conduct rounds at a hospital.

Courtesy UC Davis Health

Her colleague, Mark C. Henderson, MD, MACP, described Dr. Fitzgerald as being “extremely dedicated to each patient,” having taken care of many of them for decades. Her will to find a way to practice with severe physical limitations exemplified this dedication, said Dr. Henderson, who worked in the hospital alongside her, including handing over patients to her.

Dr. Fitzgerald died on Dec. 3, 2021, at 78 years, after working in a career spanning 6 decades, including actively practicing internal medicine at UC Davis Medical Center for 40 years.

Her career also included working as a medical educator, influencing several people interviewed for this story in that role, and advising the staff of Internal Medicine News for more than 3 decades.

“Faith Fitzgerald was an incredible teacher and mentor for so many people,” noted Robert H. Hopkins Jr., MD, who practices general internal medicine and med-peds at the University of Arkansans for Medical Sciences, Little Rock and is a member of the editorial advisory board of Internal Medicine News.
 

‘The patient and the next generation’ were always in mind

A contributor to Dr. Fitzgerald’s success as an educator was her dogged commitment to her patients, said Dr. Henderson, who is associate dean for admissions at the University of California, Davis, and professor and vice chair for education in the department of internal medicine. The latter of these positions was previously held by Dr. Fitzgerald.

“She always arrived early for hospital rounds, often waking up her patients,” he said. “She evolved this practice to be present before all the chaos of the day ensued and honestly to spend quality of time with patients.”

“She always had two things in mind: the patient and the next generation,” Dr. Henderson continued. “A lot of times, because she had seen the patients earlier in the morning, she knew where to focus the team she was training” and “she could show her students and residents all of these interesting findings.”

“It was a very efficient way of conducting bedside teaching,” he added.

Dr. Fitzgerald taught primarily in the department of internal medicine at UC Davis Health. She joined the faculty of that school in 1980. Her 38-year-long career there included serving as residency program director for nearly 20 years, chief of general medicine, vice chair for education, and the medical school’s first associate dean for humanities and bioethics.

Several people who knew Dr. Fitzgerald well also attributed her effectiveness as a teacher and a doctor to the kindness she showed all people no matter their background or station in life.

“Every patient she saw in clinic, she booked for an hour ‘til the day she left UC Davis,” noted Carmelina Raffetto, Dr. Fitzgerald’s closest friend and former administrative assistant, during UC Davis Health’s virtual memorial ceremony for Dr. Fitzgerald.

“Her patients all had her phone number, her pager. ... She loved teaching, she loved her patients, and she loved staff.

“She treated all of us equally. Whether you were in housekeeping or in the cafeteria, or if you were just walking down the hall, she had kind words and she never wanted anyone to feel that they weren’t’ special,” added Ms. Raffetto, who is currently executive director of the Northern California American College of Physicians chapter.

Throughout her career, she received over three dozen teaching awards, according to a statement from UC Davis. In 2002, for example, Dr. Fitzgerald received the Alpha Omega Alpha medical honor society’s Robert J. Glaser Award for providing medical students with an outstanding educational experience. Additional teaching awards included the American College of Physicians Distinguished Teacher Award, the California Medical Association Golden Apple Award and the UC San Francisco Gold Headed Cane.

She also received awards from UC Davis, including the Hibbard Williams Lifetime Achievement award, the Tupper Award for Excellence in Teaching and the UC Davis School of Medicine Golden Apple Award. She was also chosen as the UC Davis Senior Class Outstanding Clinical Teacher seven times and was named the Department of Medicine Distinguished Faculty Teacher on four separate occasions, the statement said.
 

Her early life and family

Dr. Fitzgerald was born in Boston on Sept. 24, 1943, and “knew from early childhood that she would be a physician,” according to her biography on Changing the Face of Medicine.

She completed undergraduate studies at the University of California, Santa Barbara. She graduated from the University of California, San Francisco, in 1969 and completed her residency in internal medicine at the same institution. In addition to teaching at UC Davis, Dr. Fitzgerald served as assistant professor of medicine at University of Michigan, Ann Arbor, for 2 years early in her career.

Dr. Fitzgerald is survived by her brother, Sean, and sister-in-law, Deborah Fitzgerald. Dr. Fitzgerald lived with and cared for her mother, Irene Fitzgerald – who passed away in 2005 – for more than a decade.

Dr. Fitzgerald asked for any donations in her memory to be used to establish scholarships for medical students with financial need, as she had been supported by scholarship money long ago while a student at the University of California. Donations to the Faith Fitzgerald, MD, Medical Student Scholarship Fund can be made here.

During her final years practicing medicine, the internist Faith Thayer Fitzgerald, MD, glided from room to room on a razor scooter at UC Davis Medical Center in Sacramento, Calif, her colleague recalled.

Dr. Fitzgerald adopted this means of transportation to allow her to examine and talk to her patients, following a hip injury and surgery, which left her unable to do the amount of walking typically required to conduct rounds at a hospital.

Courtesy UC Davis Health

Her colleague, Mark C. Henderson, MD, MACP, described Dr. Fitzgerald as being “extremely dedicated to each patient,” having taken care of many of them for decades. Her will to find a way to practice with severe physical limitations exemplified this dedication, said Dr. Henderson, who worked in the hospital alongside her, including handing over patients to her.

Dr. Fitzgerald died on Dec. 3, 2021, at 78 years, after working in a career spanning 6 decades, including actively practicing internal medicine at UC Davis Medical Center for 40 years.

Her career also included working as a medical educator, influencing several people interviewed for this story in that role, and advising the staff of Internal Medicine News for more than 3 decades.

“Faith Fitzgerald was an incredible teacher and mentor for so many people,” noted Robert H. Hopkins Jr., MD, who practices general internal medicine and med-peds at the University of Arkansans for Medical Sciences, Little Rock and is a member of the editorial advisory board of Internal Medicine News.
 

‘The patient and the next generation’ were always in mind

A contributor to Dr. Fitzgerald’s success as an educator was her dogged commitment to her patients, said Dr. Henderson, who is associate dean for admissions at the University of California, Davis, and professor and vice chair for education in the department of internal medicine. The latter of these positions was previously held by Dr. Fitzgerald.

“She always arrived early for hospital rounds, often waking up her patients,” he said. “She evolved this practice to be present before all the chaos of the day ensued and honestly to spend quality of time with patients.”

“She always had two things in mind: the patient and the next generation,” Dr. Henderson continued. “A lot of times, because she had seen the patients earlier in the morning, she knew where to focus the team she was training” and “she could show her students and residents all of these interesting findings.”

“It was a very efficient way of conducting bedside teaching,” he added.

Dr. Fitzgerald taught primarily in the department of internal medicine at UC Davis Health. She joined the faculty of that school in 1980. Her 38-year-long career there included serving as residency program director for nearly 20 years, chief of general medicine, vice chair for education, and the medical school’s first associate dean for humanities and bioethics.

Several people who knew Dr. Fitzgerald well also attributed her effectiveness as a teacher and a doctor to the kindness she showed all people no matter their background or station in life.

“Every patient she saw in clinic, she booked for an hour ‘til the day she left UC Davis,” noted Carmelina Raffetto, Dr. Fitzgerald’s closest friend and former administrative assistant, during UC Davis Health’s virtual memorial ceremony for Dr. Fitzgerald.

“Her patients all had her phone number, her pager. ... She loved teaching, she loved her patients, and she loved staff.

“She treated all of us equally. Whether you were in housekeeping or in the cafeteria, or if you were just walking down the hall, she had kind words and she never wanted anyone to feel that they weren’t’ special,” added Ms. Raffetto, who is currently executive director of the Northern California American College of Physicians chapter.

Throughout her career, she received over three dozen teaching awards, according to a statement from UC Davis. In 2002, for example, Dr. Fitzgerald received the Alpha Omega Alpha medical honor society’s Robert J. Glaser Award for providing medical students with an outstanding educational experience. Additional teaching awards included the American College of Physicians Distinguished Teacher Award, the California Medical Association Golden Apple Award and the UC San Francisco Gold Headed Cane.

She also received awards from UC Davis, including the Hibbard Williams Lifetime Achievement award, the Tupper Award for Excellence in Teaching and the UC Davis School of Medicine Golden Apple Award. She was also chosen as the UC Davis Senior Class Outstanding Clinical Teacher seven times and was named the Department of Medicine Distinguished Faculty Teacher on four separate occasions, the statement said.
 

Her early life and family

Dr. Fitzgerald was born in Boston on Sept. 24, 1943, and “knew from early childhood that she would be a physician,” according to her biography on Changing the Face of Medicine.

She completed undergraduate studies at the University of California, Santa Barbara. She graduated from the University of California, San Francisco, in 1969 and completed her residency in internal medicine at the same institution. In addition to teaching at UC Davis, Dr. Fitzgerald served as assistant professor of medicine at University of Michigan, Ann Arbor, for 2 years early in her career.

Dr. Fitzgerald is survived by her brother, Sean, and sister-in-law, Deborah Fitzgerald. Dr. Fitzgerald lived with and cared for her mother, Irene Fitzgerald – who passed away in 2005 – for more than a decade.

Dr. Fitzgerald asked for any donations in her memory to be used to establish scholarships for medical students with financial need, as she had been supported by scholarship money long ago while a student at the University of California. Donations to the Faith Fitzgerald, MD, Medical Student Scholarship Fund can be made here.

My inspiration to write about cupping this month stems from the perception that everyone seems to be talking about it, from a facialist who suggested it for me to a coworker who swears by cupping to treat her allergies. Cupping is by no means a novel procedure. Its use as a health therapy dates back thousands of years to ancient Egypt (1500 BCE), ancient Greece (described by Hippocrates), ancient Rome (described by the Greek physician Galen), China (during the Han dynasty, 206 BCE to 220 CE) and traditional Islamic culture.¹ Over the past decade, the popularity of this ancient procedure has been increasing in the United States.¹ Cupping has been applied as a remedy for various dermatologic and medical conditions, including herpes zoster, headaches, diminished appetite, maldigestion, abscess evacuation, narcolepsy, pain, fever, dysmenorrhea, and gout.^1,2

Theories on the mechanism(s) of action

The practice of cupping is differentiated into dry and wet cupping.^1,2 Traditionally, with dry cupping, a flame is applied to heat the air inside a thick glass cup (rather than the cup itself).¹ The cup is placed on the skin surface, and negative pressure suctions the skin into the cup. Wet cupping differs mainly from dry cupping in that it involves blood-letting. Cups made of either silicone or glass of varying size and shapes are used. Modern adaptations to cupping include needle, herbal, and pulsatile cupping, as well as a “moving cupping” technique (vs. traditionally stationary cups).¹

Thinkstock

There are several theories, many of which are derived from the nondermatologic literature (that is, pain management), as to how cupping may deliver a clinical benefit. Some theories are based in scientific and medical principles, whereas other theories are more whimsical – specifically, that cupping draws out evil spirits.² Studies of dry cupping have suggested that the procedure results in increased oxygenation of muscles via a local increase in oxygenated hemoglobin, which may help improve muscular activity and reduce pain.¹ As theorized by Lowe in 2017, negative pressure exerted by dry cupping leads to stretching and dilation of capillaries, which increases blood flow.³ Wet cupping has been shown to increase heat shock protein 70 (HSP70) and beta-endorphin expression in rat models, which is thought to facilitate pain management.1 Removal of oxidants and reduction of reactive oxygen species in the blood is believed to be among the benefits of wet cupping.¹
 

Cupping in general dermatology

While cupping has been used to treat a wide array of medical conditions, the ancient practice has been utilized in dermatology as a therapy mainly for herpes zoster and associated postherpetic neuralgia, as well as various inflammatory conditions.

Herpes zoster

In 2010, Cao et al. reported on their systematic review of wet cupping after completing searches of multiple databases (that is, PubMed, the Cochrane Library [Issue 3, 2008], China Network Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database). They identified eight randomized controlled trials involving 651 patients, with meta-analyses revealing that wet cupping performed better than medications in terms of the number of “cured” patients, number of patients with improved symptoms, and a lower incidence of postherpetic neuralgia. Wet cupping, in addition to medication, was also found to be superior to medication alone in multiple patients. The researchers concluded that wet cupping appears to effectively treat herpes zoster.⁴ However, the study failed to identify which medications were used to treat herpes zoster. In the United States, common medications for herpes zoster include acyclovir, valacyclovir, steroids, gabapentin, and other neuromodulators. Without knowing which medications were used, it is difficult to compare cupping to medication in terms of efficacy in treating herpes zoster.

Urticaria

Urticaria (hives) is an inflammatory skin condition that can be very uncomfortable for patients but often resolves without intervention within several months after onset. In 2001, Li and Ding reported on the treatment with cupping of 40 patients with urticaria. The cure rate among the treatment group was cited as 55%, compared with 30% in the control group, who were treated with a traditional Chinese remedy and an unidentified first-generation antihistamine.^1,5 In 2020, Xiao et al. conducted a systematic review and meta-analysis of cupping therapy for patients with chronic urticaria. They identified 13 comparisons from 12 randomized controlled trials involving 842 subjects. The investigators found no significant differences between wet cupping and medication usage. They also found that cupping combined with antihistamine treatment was superior to antihistamines alone, and cupping therapy with acupuncture was more effective than acupuncture alone. The investigators did call for caution, citing the poor quality of the studies reviewed.⁶

It is important to note that it is difficult to attribute resolution of urticaria to the use of cupping given the self-resolution often associated with this condition. Antihistamines are the mainstay of therapy for urticaria, but in my personal experience, patients are not entirely satisfied with the level of symptom control with antihistamines alone and often search for alternative therapies to control the pesky hives and associated itch. In 2014, omalizumab (Xolair) was approved for treating chronic idiopathic urticaria, which has helped patients control symptoms of chronic idiopathic urticaria without needing to take antihistamines. There was no indication that the studies reviewed by Xiao et al. compared cupping against this new effective treatment. Therefore, these studies comparing cupping to medical management are outdated.

Acne, eczema, and psoriasis

Soliman’s 2018 review of cupping in dermatology included a few studies on these common cutaneous conditions. For instance, a 2013 single-blind prospective study by Xu et al. reported on the results of patients with moderate acne who received wet cupping (in the form of prickling bloodletting) twice weekly for 6 weeks.⁷ They reported that patients demonstrated improvement in the global acne grading system (GAGS) score by the end of the trial.^1,7 Unfortunately, cupping was not compared with standard acne treatments (that is, benzoyl peroxide, topical and oral antibiotics, isotretinoin, topical retinoids, spironolactone).

In evaluating cupping for acute eczema, wet cupping was compared with oral loratadine and topical ointments in a 2007 study by Yao and Li. They divided 88 cases into treatment and control groups, with the former group (n = 46) receiving bloodletting puncturing and cupping and the control group (n = 42) receiving oral loratadine and topical Pairuisong (an herbal ointment used in Chinese medicine). The investigators observed no significant difference in total effective rates but a superior difference in the rates of responses that were considered “cured” and “markedly effective” in favor of the cupping treatment.^1,8 However, a case report by Hon et al. has indicated that cupping therapy may be associated with more harm than benefit when used as an eczema treatment.^1,9

In addition, it is important to note that the past 5 years have been gamechanging in the management of chronic eczema in terms of the array of novel and effective therapies (e.g., dupilumab and JAK inhibitors) and chronic moderate-to-severe eczema has become very treatable. Similarly, acute eczema is often successfully managed with topical steroids, calcineurin inhibitors, and emollients. As such, there is no compelling reason to consider an unproven treatment such as cupping.

In 2020, Xing et al. reviewed 16 randomized controlled trials assessing the use of “moving cupping” for plaque psoriasis, with 1,164 patients meeting inclusion criteria. Moving cupping was found to be significantly more effective than “no-moving” cupping therapy, and moving cupping, combined with medications, performed better than medications alone.¹⁰ None of the trials evaluated in this study included randomized controlled trials that compared patients using any of the more modern psoriasis medications, specifically biologics. And, again, the studies evaluated were not of the highest quality.

The data that support cupping, as summarized above, are based mostly on case reports, and strong double-blind prospective studies are lacking. Additionally, most of the studies cited gauged the efficacy of cupping using qualitative endpoints, rather than standardized quantitative endpoints and scales. Moreover, spontaneous remission of various dermatoses can occur, or they can improve over time, including acute eczema, psoriasis, and, especially, urticaria.
 

Adverse effects of cupping

Often alternative therapies are seen as “benign” and without adverse effects. However, complications can result from cupping. Trauma can be induced from the cupping itself by damaging superficial blood vessels and causing bruising.^1,11 Blistering can also occur secondary to the suction effect, and the epidermal and dermal layers of the skin can be separated.^1,11 Further, burns and discoloration have also been noted secondary to heat, trauma, and post inflammatory pigmentary changes.^1,11 Another risk of cupping is the Koebner phenomenon, which occurs with psoriasis, with new lesions appearing in traumatized skin.¹² Other adverse outcomes that have been reported with cupping include reactivation of herpes simplex virus secondary to skin trauma, iron deficiency anemia (secondary to blood loss), panniculitis, infections, and residual marks mistaken for signs of child abuse.^1,11

Cupping in aesthetic dermatology

Facial cupping, a distinct practice from body cupping used to treat general dermatology conditions described previously, is also increasing in popularity. This practice is usually conducted in association with a facial or facial acupuncture by an aesthetician or other licensed professional. It can also be performed using at-home kits. The marketing claims for facial cupping cite improved tightening and contouring of facial skin, increased facial microcirculation and collagen synthesis, and enhanced lymphatic flow to aid with facial puffiness or swelling. One supposed mechanism for these benefits is that cupping increases blood flow. Interestingly, there was a 2020 animal study in which photoacoustic imaging of a mouse ear revealed increased temporary blood flow in the cupping microenvironment.¹³ Currently, however, there is no evidence in the English scientific literature that supports facial cupping. The benefits attributed to facial cupping for aesthetic purposes have emerged only in personal anecdotes. The temporary increase in blood flow may induce inflammation and swelling that adds volume to the face and temporarily diminishes wrinkles. However, this temporary plumpness may be associated with adverse effects, such as local trauma, irritation, bruising, postinflammatory pigmentary alteration, or even herpes reactivation. In my opinion, the possible adverse effects of cupping outweigh any potential benefit, especially given the insufficient evidence supporting the utility of cupping for cosmetic enhancement.

Summary

There is increasing interest among patients to incorporate complementary and alternative medicine – including the ancient tradition of cupping – in managing medical dermatologic conditions. However, current evidence supporting cupping as an effective therapeutic strategy is not strong, with most studies to date appearing to be of poor quality or not sufficiently convincing to displace standard therapies. Our medical strategies for managing chronic dermatologic conditions, particularly inflammatory disorders, continue to improve from both a safety and a proven efficacy standpoint. Therefore, I would not forgo medical management in favor of cupping. While cupping can be used as an adjunct therapy, I would caution patients about possible adverse side effects. In the aesthetic world, cupping is also gaining popularity, but this trend is also not supported by current evidence or studies, at least in the Western literature.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Write to her at [email protected] or message her on Instragram @DrChloeGoldman. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other disclosures.

References

1. Soliman Y et al. Acta Dermatovenerol Alp Pannonica Adriat. 2018 Jun;27(2):103-7.

2. França K and Lotti T. Advances in Integrative Dermatology. John Wiley & Sons, 2019.

3. Lowe DT. Complement Ther Clin Pract. 2017 Nov;29:162-8.

4.Cao H et al. Altern Ther Health Med. 2010 Nov-Dec;16(6):48-54.

5. Li L and Ding J. J Tradit Chin Med. 2001 Mar;21(1):37-8.

6. Xiao XJ et al. J Integr Med. 2020 Jul;18(4):303-12.

7. Xu J et al. J Tradit Chin Med. 2013 Dec;33(6):752-6.

8. Yao J et al. Zhongguo Zhen Jiu. 2007; Jun;27(6):424-6.

9. Hon KL et al. Case Rep Pediatr. 2013;2013:605829.

10. Xing M et al. Medicine (Baltimore). 2020 Oct 9;99(41):e22539.

11. Kim TH et al. Eur J Integr Med. 2014 Aug 1;6(4):434-40.

12. Vender R and Vender R. J Cutan Med Surg. 2015 May-Jun;19(3):320-2.

13. Zhou Y et al. Biomed Opt Express. 2020 Apr 6;11(5):2394-401.

This article was updated 4/25/22.

My inspiration to write about cupping this month stems from the perception that everyone seems to be talking about it, from a facialist who suggested it for me to a coworker who swears by cupping to treat her allergies. Cupping is by no means a novel procedure. Its use as a health therapy dates back thousands of years to ancient Egypt (1500 BCE), ancient Greece (described by Hippocrates), ancient Rome (described by the Greek physician Galen), China (during the Han dynasty, 206 BCE to 220 CE) and traditional Islamic culture.¹ Over the past decade, the popularity of this ancient procedure has been increasing in the United States.¹ Cupping has been applied as a remedy for various dermatologic and medical conditions, including herpes zoster, headaches, diminished appetite, maldigestion, abscess evacuation, narcolepsy, pain, fever, dysmenorrhea, and gout.^1,2

Theories on the mechanism(s) of action

The practice of cupping is differentiated into dry and wet cupping.^1,2 Traditionally, with dry cupping, a flame is applied to heat the air inside a thick glass cup (rather than the cup itself).¹ The cup is placed on the skin surface, and negative pressure suctions the skin into the cup. Wet cupping differs mainly from dry cupping in that it involves blood-letting. Cups made of either silicone or glass of varying size and shapes are used. Modern adaptations to cupping include needle, herbal, and pulsatile cupping, as well as a “moving cupping” technique (vs. traditionally stationary cups).¹

Thinkstock

There are several theories, many of which are derived from the nondermatologic literature (that is, pain management), as to how cupping may deliver a clinical benefit. Some theories are based in scientific and medical principles, whereas other theories are more whimsical – specifically, that cupping draws out evil spirits.² Studies of dry cupping have suggested that the procedure results in increased oxygenation of muscles via a local increase in oxygenated hemoglobin, which may help improve muscular activity and reduce pain.¹ As theorized by Lowe in 2017, negative pressure exerted by dry cupping leads to stretching and dilation of capillaries, which increases blood flow.³ Wet cupping has been shown to increase heat shock protein 70 (HSP70) and beta-endorphin expression in rat models, which is thought to facilitate pain management.1 Removal of oxidants and reduction of reactive oxygen species in the blood is believed to be among the benefits of wet cupping.¹
 

Cupping in general dermatology

While cupping has been used to treat a wide array of medical conditions, the ancient practice has been utilized in dermatology as a therapy mainly for herpes zoster and associated postherpetic neuralgia, as well as various inflammatory conditions.

Herpes zoster

In 2010, Cao et al. reported on their systematic review of wet cupping after completing searches of multiple databases (that is, PubMed, the Cochrane Library [Issue 3, 2008], China Network Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database). They identified eight randomized controlled trials involving 651 patients, with meta-analyses revealing that wet cupping performed better than medications in terms of the number of “cured” patients, number of patients with improved symptoms, and a lower incidence of postherpetic neuralgia. Wet cupping, in addition to medication, was also found to be superior to medication alone in multiple patients. The researchers concluded that wet cupping appears to effectively treat herpes zoster.⁴ However, the study failed to identify which medications were used to treat herpes zoster. In the United States, common medications for herpes zoster include acyclovir, valacyclovir, steroids, gabapentin, and other neuromodulators. Without knowing which medications were used, it is difficult to compare cupping to medication in terms of efficacy in treating herpes zoster.

Urticaria

Urticaria (hives) is an inflammatory skin condition that can be very uncomfortable for patients but often resolves without intervention within several months after onset. In 2001, Li and Ding reported on the treatment with cupping of 40 patients with urticaria. The cure rate among the treatment group was cited as 55%, compared with 30% in the control group, who were treated with a traditional Chinese remedy and an unidentified first-generation antihistamine.^1,5 In 2020, Xiao et al. conducted a systematic review and meta-analysis of cupping therapy for patients with chronic urticaria. They identified 13 comparisons from 12 randomized controlled trials involving 842 subjects. The investigators found no significant differences between wet cupping and medication usage. They also found that cupping combined with antihistamine treatment was superior to antihistamines alone, and cupping therapy with acupuncture was more effective than acupuncture alone. The investigators did call for caution, citing the poor quality of the studies reviewed.⁶

It is important to note that it is difficult to attribute resolution of urticaria to the use of cupping given the self-resolution often associated with this condition. Antihistamines are the mainstay of therapy for urticaria, but in my personal experience, patients are not entirely satisfied with the level of symptom control with antihistamines alone and often search for alternative therapies to control the pesky hives and associated itch. In 2014, omalizumab (Xolair) was approved for treating chronic idiopathic urticaria, which has helped patients control symptoms of chronic idiopathic urticaria without needing to take antihistamines. There was no indication that the studies reviewed by Xiao et al. compared cupping against this new effective treatment. Therefore, these studies comparing cupping to medical management are outdated.

Acne, eczema, and psoriasis

Soliman’s 2018 review of cupping in dermatology included a few studies on these common cutaneous conditions. For instance, a 2013 single-blind prospective study by Xu et al. reported on the results of patients with moderate acne who received wet cupping (in the form of prickling bloodletting) twice weekly for 6 weeks.⁷ They reported that patients demonstrated improvement in the global acne grading system (GAGS) score by the end of the trial.^1,7 Unfortunately, cupping was not compared with standard acne treatments (that is, benzoyl peroxide, topical and oral antibiotics, isotretinoin, topical retinoids, spironolactone).

In evaluating cupping for acute eczema, wet cupping was compared with oral loratadine and topical ointments in a 2007 study by Yao and Li. They divided 88 cases into treatment and control groups, with the former group (n = 46) receiving bloodletting puncturing and cupping and the control group (n = 42) receiving oral loratadine and topical Pairuisong (an herbal ointment used in Chinese medicine). The investigators observed no significant difference in total effective rates but a superior difference in the rates of responses that were considered “cured” and “markedly effective” in favor of the cupping treatment.^1,8 However, a case report by Hon et al. has indicated that cupping therapy may be associated with more harm than benefit when used as an eczema treatment.^1,9

In addition, it is important to note that the past 5 years have been gamechanging in the management of chronic eczema in terms of the array of novel and effective therapies (e.g., dupilumab and JAK inhibitors) and chronic moderate-to-severe eczema has become very treatable. Similarly, acute eczema is often successfully managed with topical steroids, calcineurin inhibitors, and emollients. As such, there is no compelling reason to consider an unproven treatment such as cupping.

In 2020, Xing et al. reviewed 16 randomized controlled trials assessing the use of “moving cupping” for plaque psoriasis, with 1,164 patients meeting inclusion criteria. Moving cupping was found to be significantly more effective than “no-moving” cupping therapy, and moving cupping, combined with medications, performed better than medications alone.¹⁰ None of the trials evaluated in this study included randomized controlled trials that compared patients using any of the more modern psoriasis medications, specifically biologics. And, again, the studies evaluated were not of the highest quality.

The data that support cupping, as summarized above, are based mostly on case reports, and strong double-blind prospective studies are lacking. Additionally, most of the studies cited gauged the efficacy of cupping using qualitative endpoints, rather than standardized quantitative endpoints and scales. Moreover, spontaneous remission of various dermatoses can occur, or they can improve over time, including acute eczema, psoriasis, and, especially, urticaria.
 

Adverse effects of cupping

Often alternative therapies are seen as “benign” and without adverse effects. However, complications can result from cupping. Trauma can be induced from the cupping itself by damaging superficial blood vessels and causing bruising.^1,11 Blistering can also occur secondary to the suction effect, and the epidermal and dermal layers of the skin can be separated.^1,11 Further, burns and discoloration have also been noted secondary to heat, trauma, and post inflammatory pigmentary changes.^1,11 Another risk of cupping is the Koebner phenomenon, which occurs with psoriasis, with new lesions appearing in traumatized skin.¹² Other adverse outcomes that have been reported with cupping include reactivation of herpes simplex virus secondary to skin trauma, iron deficiency anemia (secondary to blood loss), panniculitis, infections, and residual marks mistaken for signs of child abuse.^1,11

Cupping in aesthetic dermatology

Facial cupping, a distinct practice from body cupping used to treat general dermatology conditions described previously, is also increasing in popularity. This practice is usually conducted in association with a facial or facial acupuncture by an aesthetician or other licensed professional. It can also be performed using at-home kits. The marketing claims for facial cupping cite improved tightening and contouring of facial skin, increased facial microcirculation and collagen synthesis, and enhanced lymphatic flow to aid with facial puffiness or swelling. One supposed mechanism for these benefits is that cupping increases blood flow. Interestingly, there was a 2020 animal study in which photoacoustic imaging of a mouse ear revealed increased temporary blood flow in the cupping microenvironment.¹³ Currently, however, there is no evidence in the English scientific literature that supports facial cupping. The benefits attributed to facial cupping for aesthetic purposes have emerged only in personal anecdotes. The temporary increase in blood flow may induce inflammation and swelling that adds volume to the face and temporarily diminishes wrinkles. However, this temporary plumpness may be associated with adverse effects, such as local trauma, irritation, bruising, postinflammatory pigmentary alteration, or even herpes reactivation. In my opinion, the possible adverse effects of cupping outweigh any potential benefit, especially given the insufficient evidence supporting the utility of cupping for cosmetic enhancement.

Summary

There is increasing interest among patients to incorporate complementary and alternative medicine – including the ancient tradition of cupping – in managing medical dermatologic conditions. However, current evidence supporting cupping as an effective therapeutic strategy is not strong, with most studies to date appearing to be of poor quality or not sufficiently convincing to displace standard therapies. Our medical strategies for managing chronic dermatologic conditions, particularly inflammatory disorders, continue to improve from both a safety and a proven efficacy standpoint. Therefore, I would not forgo medical management in favor of cupping. While cupping can be used as an adjunct therapy, I would caution patients about possible adverse side effects. In the aesthetic world, cupping is also gaining popularity, but this trend is also not supported by current evidence or studies, at least in the Western literature.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Write to her at [email protected] or message her on Instragram @DrChloeGoldman. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other disclosures.

References

1. Soliman Y et al. Acta Dermatovenerol Alp Pannonica Adriat. 2018 Jun;27(2):103-7.

2. França K and Lotti T. Advances in Integrative Dermatology. John Wiley & Sons, 2019.

3. Lowe DT. Complement Ther Clin Pract. 2017 Nov;29:162-8.

4.Cao H et al. Altern Ther Health Med. 2010 Nov-Dec;16(6):48-54.

5. Li L and Ding J. J Tradit Chin Med. 2001 Mar;21(1):37-8.

6. Xiao XJ et al. J Integr Med. 2020 Jul;18(4):303-12.

7. Xu J et al. J Tradit Chin Med. 2013 Dec;33(6):752-6.

8. Yao J et al. Zhongguo Zhen Jiu. 2007; Jun;27(6):424-6.

9. Hon KL et al. Case Rep Pediatr. 2013;2013:605829.

10. Xing M et al. Medicine (Baltimore). 2020 Oct 9;99(41):e22539.

11. Kim TH et al. Eur J Integr Med. 2014 Aug 1;6(4):434-40.

12. Vender R and Vender R. J Cutan Med Surg. 2015 May-Jun;19(3):320-2.

13. Zhou Y et al. Biomed Opt Express. 2020 Apr 6;11(5):2394-401.

This article was updated 4/25/22.

My inspiration to write about cupping this month stems from the perception that everyone seems to be talking about it, from a facialist who suggested it for me to a coworker who swears by cupping to treat her allergies. Cupping is by no means a novel procedure. Its use as a health therapy dates back thousands of years to ancient Egypt (1500 BCE), ancient Greece (described by Hippocrates), ancient Rome (described by the Greek physician Galen), China (during the Han dynasty, 206 BCE to 220 CE) and traditional Islamic culture.¹ Over the past decade, the popularity of this ancient procedure has been increasing in the United States.¹ Cupping has been applied as a remedy for various dermatologic and medical conditions, including herpes zoster, headaches, diminished appetite, maldigestion, abscess evacuation, narcolepsy, pain, fever, dysmenorrhea, and gout.^1,2

Theories on the mechanism(s) of action

The practice of cupping is differentiated into dry and wet cupping.^1,2 Traditionally, with dry cupping, a flame is applied to heat the air inside a thick glass cup (rather than the cup itself).¹ The cup is placed on the skin surface, and negative pressure suctions the skin into the cup. Wet cupping differs mainly from dry cupping in that it involves blood-letting. Cups made of either silicone or glass of varying size and shapes are used. Modern adaptations to cupping include needle, herbal, and pulsatile cupping, as well as a “moving cupping” technique (vs. traditionally stationary cups).¹

Thinkstock

There are several theories, many of which are derived from the nondermatologic literature (that is, pain management), as to how cupping may deliver a clinical benefit. Some theories are based in scientific and medical principles, whereas other theories are more whimsical – specifically, that cupping draws out evil spirits.² Studies of dry cupping have suggested that the procedure results in increased oxygenation of muscles via a local increase in oxygenated hemoglobin, which may help improve muscular activity and reduce pain.¹ As theorized by Lowe in 2017, negative pressure exerted by dry cupping leads to stretching and dilation of capillaries, which increases blood flow.³ Wet cupping has been shown to increase heat shock protein 70 (HSP70) and beta-endorphin expression in rat models, which is thought to facilitate pain management.1 Removal of oxidants and reduction of reactive oxygen species in the blood is believed to be among the benefits of wet cupping.¹
 

Cupping in general dermatology

While cupping has been used to treat a wide array of medical conditions, the ancient practice has been utilized in dermatology as a therapy mainly for herpes zoster and associated postherpetic neuralgia, as well as various inflammatory conditions.

Herpes zoster

In 2010, Cao et al. reported on their systematic review of wet cupping after completing searches of multiple databases (that is, PubMed, the Cochrane Library [Issue 3, 2008], China Network Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database). They identified eight randomized controlled trials involving 651 patients, with meta-analyses revealing that wet cupping performed better than medications in terms of the number of “cured” patients, number of patients with improved symptoms, and a lower incidence of postherpetic neuralgia. Wet cupping, in addition to medication, was also found to be superior to medication alone in multiple patients. The researchers concluded that wet cupping appears to effectively treat herpes zoster.⁴ However, the study failed to identify which medications were used to treat herpes zoster. In the United States, common medications for herpes zoster include acyclovir, valacyclovir, steroids, gabapentin, and other neuromodulators. Without knowing which medications were used, it is difficult to compare cupping to medication in terms of efficacy in treating herpes zoster.

Urticaria

Urticaria (hives) is an inflammatory skin condition that can be very uncomfortable for patients but often resolves without intervention within several months after onset. In 2001, Li and Ding reported on the treatment with cupping of 40 patients with urticaria. The cure rate among the treatment group was cited as 55%, compared with 30% in the control group, who were treated with a traditional Chinese remedy and an unidentified first-generation antihistamine.^1,5 In 2020, Xiao et al. conducted a systematic review and meta-analysis of cupping therapy for patients with chronic urticaria. They identified 13 comparisons from 12 randomized controlled trials involving 842 subjects. The investigators found no significant differences between wet cupping and medication usage. They also found that cupping combined with antihistamine treatment was superior to antihistamines alone, and cupping therapy with acupuncture was more effective than acupuncture alone. The investigators did call for caution, citing the poor quality of the studies reviewed.⁶

It is important to note that it is difficult to attribute resolution of urticaria to the use of cupping given the self-resolution often associated with this condition. Antihistamines are the mainstay of therapy for urticaria, but in my personal experience, patients are not entirely satisfied with the level of symptom control with antihistamines alone and often search for alternative therapies to control the pesky hives and associated itch. In 2014, omalizumab (Xolair) was approved for treating chronic idiopathic urticaria, which has helped patients control symptoms of chronic idiopathic urticaria without needing to take antihistamines. There was no indication that the studies reviewed by Xiao et al. compared cupping against this new effective treatment. Therefore, these studies comparing cupping to medical management are outdated.

Acne, eczema, and psoriasis

Soliman’s 2018 review of cupping in dermatology included a few studies on these common cutaneous conditions. For instance, a 2013 single-blind prospective study by Xu et al. reported on the results of patients with moderate acne who received wet cupping (in the form of prickling bloodletting) twice weekly for 6 weeks.⁷ They reported that patients demonstrated improvement in the global acne grading system (GAGS) score by the end of the trial.^1,7 Unfortunately, cupping was not compared with standard acne treatments (that is, benzoyl peroxide, topical and oral antibiotics, isotretinoin, topical retinoids, spironolactone).

In evaluating cupping for acute eczema, wet cupping was compared with oral loratadine and topical ointments in a 2007 study by Yao and Li. They divided 88 cases into treatment and control groups, with the former group (n = 46) receiving bloodletting puncturing and cupping and the control group (n = 42) receiving oral loratadine and topical Pairuisong (an herbal ointment used in Chinese medicine). The investigators observed no significant difference in total effective rates but a superior difference in the rates of responses that were considered “cured” and “markedly effective” in favor of the cupping treatment.^1,8 However, a case report by Hon et al. has indicated that cupping therapy may be associated with more harm than benefit when used as an eczema treatment.^1,9

In addition, it is important to note that the past 5 years have been gamechanging in the management of chronic eczema in terms of the array of novel and effective therapies (e.g., dupilumab and JAK inhibitors) and chronic moderate-to-severe eczema has become very treatable. Similarly, acute eczema is often successfully managed with topical steroids, calcineurin inhibitors, and emollients. As such, there is no compelling reason to consider an unproven treatment such as cupping.

In 2020, Xing et al. reviewed 16 randomized controlled trials assessing the use of “moving cupping” for plaque psoriasis, with 1,164 patients meeting inclusion criteria. Moving cupping was found to be significantly more effective than “no-moving” cupping therapy, and moving cupping, combined with medications, performed better than medications alone.¹⁰ None of the trials evaluated in this study included randomized controlled trials that compared patients using any of the more modern psoriasis medications, specifically biologics. And, again, the studies evaluated were not of the highest quality.

The data that support cupping, as summarized above, are based mostly on case reports, and strong double-blind prospective studies are lacking. Additionally, most of the studies cited gauged the efficacy of cupping using qualitative endpoints, rather than standardized quantitative endpoints and scales. Moreover, spontaneous remission of various dermatoses can occur, or they can improve over time, including acute eczema, psoriasis, and, especially, urticaria.
 

Adverse effects of cupping

Often alternative therapies are seen as “benign” and without adverse effects. However, complications can result from cupping. Trauma can be induced from the cupping itself by damaging superficial blood vessels and causing bruising.^1,11 Blistering can also occur secondary to the suction effect, and the epidermal and dermal layers of the skin can be separated.^1,11 Further, burns and discoloration have also been noted secondary to heat, trauma, and post inflammatory pigmentary changes.^1,11 Another risk of cupping is the Koebner phenomenon, which occurs with psoriasis, with new lesions appearing in traumatized skin.¹² Other adverse outcomes that have been reported with cupping include reactivation of herpes simplex virus secondary to skin trauma, iron deficiency anemia (secondary to blood loss), panniculitis, infections, and residual marks mistaken for signs of child abuse.^1,11

Cupping in aesthetic dermatology

Facial cupping, a distinct practice from body cupping used to treat general dermatology conditions described previously, is also increasing in popularity. This practice is usually conducted in association with a facial or facial acupuncture by an aesthetician or other licensed professional. It can also be performed using at-home kits. The marketing claims for facial cupping cite improved tightening and contouring of facial skin, increased facial microcirculation and collagen synthesis, and enhanced lymphatic flow to aid with facial puffiness or swelling. One supposed mechanism for these benefits is that cupping increases blood flow. Interestingly, there was a 2020 animal study in which photoacoustic imaging of a mouse ear revealed increased temporary blood flow in the cupping microenvironment.¹³ Currently, however, there is no evidence in the English scientific literature that supports facial cupping. The benefits attributed to facial cupping for aesthetic purposes have emerged only in personal anecdotes. The temporary increase in blood flow may induce inflammation and swelling that adds volume to the face and temporarily diminishes wrinkles. However, this temporary plumpness may be associated with adverse effects, such as local trauma, irritation, bruising, postinflammatory pigmentary alteration, or even herpes reactivation. In my opinion, the possible adverse effects of cupping outweigh any potential benefit, especially given the insufficient evidence supporting the utility of cupping for cosmetic enhancement.

Summary

There is increasing interest among patients to incorporate complementary and alternative medicine – including the ancient tradition of cupping – in managing medical dermatologic conditions. However, current evidence supporting cupping as an effective therapeutic strategy is not strong, with most studies to date appearing to be of poor quality or not sufficiently convincing to displace standard therapies. Our medical strategies for managing chronic dermatologic conditions, particularly inflammatory disorders, continue to improve from both a safety and a proven efficacy standpoint. Therefore, I would not forgo medical management in favor of cupping. While cupping can be used as an adjunct therapy, I would caution patients about possible adverse side effects. In the aesthetic world, cupping is also gaining popularity, but this trend is also not supported by current evidence or studies, at least in the Western literature.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Write to her at [email protected] or message her on Instragram @DrChloeGoldman. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other disclosures.

References

1. Soliman Y et al. Acta Dermatovenerol Alp Pannonica Adriat. 2018 Jun;27(2):103-7.

2. França K and Lotti T. Advances in Integrative Dermatology. John Wiley & Sons, 2019.

3. Lowe DT. Complement Ther Clin Pract. 2017 Nov;29:162-8.

4.Cao H et al. Altern Ther Health Med. 2010 Nov-Dec;16(6):48-54.

5. Li L and Ding J. J Tradit Chin Med. 2001 Mar;21(1):37-8.

6. Xiao XJ et al. J Integr Med. 2020 Jul;18(4):303-12.

7. Xu J et al. J Tradit Chin Med. 2013 Dec;33(6):752-6.

8. Yao J et al. Zhongguo Zhen Jiu. 2007; Jun;27(6):424-6.

9. Hon KL et al. Case Rep Pediatr. 2013;2013:605829.

10. Xing M et al. Medicine (Baltimore). 2020 Oct 9;99(41):e22539.

11. Kim TH et al. Eur J Integr Med. 2014 Aug 1;6(4):434-40.

12. Vender R and Vender R. J Cutan Med Surg. 2015 May-Jun;19(3):320-2.

13. Zhou Y et al. Biomed Opt Express. 2020 Apr 6;11(5):2394-401.

This article was updated 4/25/22.