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Survey: Lack of awareness hampers cancer prevention efforts
The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.
Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.
Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.
For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.
Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.
The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.
The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.
“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.
“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”
Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.
The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.
Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”
As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.
An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”
The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.
Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.
Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.
For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.
Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.
The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.
The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.
“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.
“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”
Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.
The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.
Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”
As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.
An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”
The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.
Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.
Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.
For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.
Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.
The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.
The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.
“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.
“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”
Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.
The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.
Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”
As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.
An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”
Patisiran (Onpattro) for ATTR cardiomyopathy gets FDA panel thumbs up
The Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration has voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy – although many panel members questioned whether the benefits are clinically meaningful.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.
Intravenously administered patisiran is already approved in the United States and Canada for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.
In the APOLLO-B trial, patisiran showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test, compared with placebo, in patients with ATTR amyloidosis with cardiomyopathy.
The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.
But in explaining her “no” vote, committee member C. Noel Bairey Merz, MD, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, said she “did not feel like there was benefit” using existing clinically relevant thresholds typically used in cardiology.
Committee chair Javed Butler, MD, MPH, Baylor Scott & White Research Institute, Dallas, who also voted no, said he “struggled” with this vote and emphasized that it “absolutely does not reflect that there is not a potential with the therapy.”
Dr. Butler said he voted no largely because he wasn’t sure whether the benefits are clinically meaningful in the context of the study design and how it was conducted. He did not have any safety concerns, which was the general feeling of the committee.
Edward Kasper, MD, Johns Hopkins University, Baltimore, who voted in favor of patisiran for ATTR amyloidosis with cardiomyopathy, said there is a “light wind for benefit and no wind for risk. So, if you’re asking do benefits outweigh the risks, the answer is yes.”
But Dr. Kasper also noted: “It would have been a more difficult question to answer: Is there clinically meaningful benefit versus risk? But that’s not what the question asked.”
In explaining his “yes” vote, Ravi Thadhani, MD, MPH, Emory University, Atlanta, said: “We’re dealing with a rare disease with few options and devastating consequences. We heard from clinicians loud and clear, and from patients for that matter, that options and alternatives are critical, and that there is a continuous decline of cardiac function and worsening of disease in a number of patients that have received the current standard of care. For me, the benefits outweigh the risks.”
Dr. Thadhani also noted that from the data provided, no benefit was shown – ”disappointingly” he lamented – for women, for Black persons, and among individuals who were receiving tafamidis, and he urged the FDA and sponsor to consider this.
The FDA has set a target action date for patisiran for ATTR amyloidosis cardiomyopathy of Oct. 8.
A version of this article first appeared on Medscape.com.
The Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration has voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy – although many panel members questioned whether the benefits are clinically meaningful.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.
Intravenously administered patisiran is already approved in the United States and Canada for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.
In the APOLLO-B trial, patisiran showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test, compared with placebo, in patients with ATTR amyloidosis with cardiomyopathy.
The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.
But in explaining her “no” vote, committee member C. Noel Bairey Merz, MD, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, said she “did not feel like there was benefit” using existing clinically relevant thresholds typically used in cardiology.
Committee chair Javed Butler, MD, MPH, Baylor Scott & White Research Institute, Dallas, who also voted no, said he “struggled” with this vote and emphasized that it “absolutely does not reflect that there is not a potential with the therapy.”
Dr. Butler said he voted no largely because he wasn’t sure whether the benefits are clinically meaningful in the context of the study design and how it was conducted. He did not have any safety concerns, which was the general feeling of the committee.
Edward Kasper, MD, Johns Hopkins University, Baltimore, who voted in favor of patisiran for ATTR amyloidosis with cardiomyopathy, said there is a “light wind for benefit and no wind for risk. So, if you’re asking do benefits outweigh the risks, the answer is yes.”
But Dr. Kasper also noted: “It would have been a more difficult question to answer: Is there clinically meaningful benefit versus risk? But that’s not what the question asked.”
In explaining his “yes” vote, Ravi Thadhani, MD, MPH, Emory University, Atlanta, said: “We’re dealing with a rare disease with few options and devastating consequences. We heard from clinicians loud and clear, and from patients for that matter, that options and alternatives are critical, and that there is a continuous decline of cardiac function and worsening of disease in a number of patients that have received the current standard of care. For me, the benefits outweigh the risks.”
Dr. Thadhani also noted that from the data provided, no benefit was shown – ”disappointingly” he lamented – for women, for Black persons, and among individuals who were receiving tafamidis, and he urged the FDA and sponsor to consider this.
The FDA has set a target action date for patisiran for ATTR amyloidosis cardiomyopathy of Oct. 8.
A version of this article first appeared on Medscape.com.
The Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration has voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy – although many panel members questioned whether the benefits are clinically meaningful.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.
Intravenously administered patisiran is already approved in the United States and Canada for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.
In the APOLLO-B trial, patisiran showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test, compared with placebo, in patients with ATTR amyloidosis with cardiomyopathy.
The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.
But in explaining her “no” vote, committee member C. Noel Bairey Merz, MD, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, said she “did not feel like there was benefit” using existing clinically relevant thresholds typically used in cardiology.
Committee chair Javed Butler, MD, MPH, Baylor Scott & White Research Institute, Dallas, who also voted no, said he “struggled” with this vote and emphasized that it “absolutely does not reflect that there is not a potential with the therapy.”
Dr. Butler said he voted no largely because he wasn’t sure whether the benefits are clinically meaningful in the context of the study design and how it was conducted. He did not have any safety concerns, which was the general feeling of the committee.
Edward Kasper, MD, Johns Hopkins University, Baltimore, who voted in favor of patisiran for ATTR amyloidosis with cardiomyopathy, said there is a “light wind for benefit and no wind for risk. So, if you’re asking do benefits outweigh the risks, the answer is yes.”
But Dr. Kasper also noted: “It would have been a more difficult question to answer: Is there clinically meaningful benefit versus risk? But that’s not what the question asked.”
In explaining his “yes” vote, Ravi Thadhani, MD, MPH, Emory University, Atlanta, said: “We’re dealing with a rare disease with few options and devastating consequences. We heard from clinicians loud and clear, and from patients for that matter, that options and alternatives are critical, and that there is a continuous decline of cardiac function and worsening of disease in a number of patients that have received the current standard of care. For me, the benefits outweigh the risks.”
Dr. Thadhani also noted that from the data provided, no benefit was shown – ”disappointingly” he lamented – for women, for Black persons, and among individuals who were receiving tafamidis, and he urged the FDA and sponsor to consider this.
The FDA has set a target action date for patisiran for ATTR amyloidosis cardiomyopathy of Oct. 8.
A version of this article first appeared on Medscape.com.
The role of social media in aesthetic trends
Recently, but I had never heard it before. Not too long afterwards, patients were asking me about it in the office, using the same terminology, and I had several calls about it in one day. When I asked one trusted patient where she’d heard this term, which seemed to be trending, she told me that she had seen it on Instagram, as an ad or a “suggested for you” post.
Whether it’s a different name or term for a cosmetic procedure or laser we use that I’ve never heard before – such as “lip flip” or trap tox (also known as “Barbie Botox”) – many of these trendy terms spread like wildfire on social media. Some of the terms may be marketing tools started and spread by doctors who perform aesthetic procedures, something I don’t recommend as it only creates confusion for patients and practitioners, similar to the confusion consumers face regarding the plethora of over-the-counter skin care options and the marketing terms used for them. Other terms and trends are also started by nonphysician or non–professionally trained providers, sometimes leading to an unsafe or misleading term for an aesthetic procedure.
Over the past few years, several articles about the impact of social media in aesthetics have been published. In one recent paper, published in 2022, Boen and Jerdan noted that 72% of people in the United States use social media, up from 5% of American adults in 2005. In the United States, they note, “YouTube is the most popular platform with 73% of adult users, followed by Facebook (69%), Instagram (37%), SnapChat (24%), and Twitter (22%). Of the sites used daily, Facebook has the most activity (74%), followed by Instagram (64%), SnapChat (63%), YouTube (51%), and Twitter (42%).” They argue that the pros of social media in aesthetic medicine include its use as an educational tool by medical professionals to educate and provide accurate information about cosmetic procedures, and that “providing factual and evidence-based medical information to the public can help to counteract the abundant misinformation that is out there.” The cons include misinformation, no credentialing verification of the provider of the information – essentially anyone can be an “influencer” – as well as the addictive nature of social media for the consumer.
Along the same lines, younger patients tend to rely more on social media in choosing treatments and providers, further perpetuating any anxiety created from misinformation and unrealistic expectations from nonmedical influencers regarding procedures, filters used on photographs, photo editing, etc., in achieving an aesthetic result.
Physicians, particularly fellowship-trained aesthetic and surgical dermatologists, plastic and reconstructive surgeons, oculoplastic surgeons, and ENT facial plastic surgeons, who have the most training, knowledge, and expertise about aesthetic procedures, often have the least amount of time to devote to education via social media, compared with nonmedical influencers. Unless sponsored, they are also not being compensated for using it as an educational tool, except for potential indirect compensation from using it as a marketing tool for themselves and their practices. In contrast, nonmedical influencers often have many followers and time to create content, and in some cases, this is their full-time job.
All in all, most authors agree that social media has been associated with an increased acceptance of cosmetic surgery and procedures. Whether it be a trend seen on social media, or viewing one’s appearance in a filtered or photoediting app, or seeing an image of how another person looks (similar to how people in magazines, films and on television, were viewed in the past), social media has piqued people’s interest in aesthetics. It remains a balance for interested physicians to help keep information about cosmetic procedures presented in a healthy, interesting, professional, and accurate manner, and in a non–time-consuming way.
Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at dermnews@mdedge.com. She had no relevant disclosures.
References
Boen M and Jerdan K. Clin Dermatol. 2022 Jan-Feb;40(1):45-8.
Chen J et al. JAMA Facial Plast Surg. 2019 Sep 1;21(5):361-7.
Chopan M et al. Plast Reconstr Surg. 2019 Apr;143(4):1259-65.
Recently, but I had never heard it before. Not too long afterwards, patients were asking me about it in the office, using the same terminology, and I had several calls about it in one day. When I asked one trusted patient where she’d heard this term, which seemed to be trending, she told me that she had seen it on Instagram, as an ad or a “suggested for you” post.
Whether it’s a different name or term for a cosmetic procedure or laser we use that I’ve never heard before – such as “lip flip” or trap tox (also known as “Barbie Botox”) – many of these trendy terms spread like wildfire on social media. Some of the terms may be marketing tools started and spread by doctors who perform aesthetic procedures, something I don’t recommend as it only creates confusion for patients and practitioners, similar to the confusion consumers face regarding the plethora of over-the-counter skin care options and the marketing terms used for them. Other terms and trends are also started by nonphysician or non–professionally trained providers, sometimes leading to an unsafe or misleading term for an aesthetic procedure.
Over the past few years, several articles about the impact of social media in aesthetics have been published. In one recent paper, published in 2022, Boen and Jerdan noted that 72% of people in the United States use social media, up from 5% of American adults in 2005. In the United States, they note, “YouTube is the most popular platform with 73% of adult users, followed by Facebook (69%), Instagram (37%), SnapChat (24%), and Twitter (22%). Of the sites used daily, Facebook has the most activity (74%), followed by Instagram (64%), SnapChat (63%), YouTube (51%), and Twitter (42%).” They argue that the pros of social media in aesthetic medicine include its use as an educational tool by medical professionals to educate and provide accurate information about cosmetic procedures, and that “providing factual and evidence-based medical information to the public can help to counteract the abundant misinformation that is out there.” The cons include misinformation, no credentialing verification of the provider of the information – essentially anyone can be an “influencer” – as well as the addictive nature of social media for the consumer.
Along the same lines, younger patients tend to rely more on social media in choosing treatments and providers, further perpetuating any anxiety created from misinformation and unrealistic expectations from nonmedical influencers regarding procedures, filters used on photographs, photo editing, etc., in achieving an aesthetic result.
Physicians, particularly fellowship-trained aesthetic and surgical dermatologists, plastic and reconstructive surgeons, oculoplastic surgeons, and ENT facial plastic surgeons, who have the most training, knowledge, and expertise about aesthetic procedures, often have the least amount of time to devote to education via social media, compared with nonmedical influencers. Unless sponsored, they are also not being compensated for using it as an educational tool, except for potential indirect compensation from using it as a marketing tool for themselves and their practices. In contrast, nonmedical influencers often have many followers and time to create content, and in some cases, this is their full-time job.
All in all, most authors agree that social media has been associated with an increased acceptance of cosmetic surgery and procedures. Whether it be a trend seen on social media, or viewing one’s appearance in a filtered or photoediting app, or seeing an image of how another person looks (similar to how people in magazines, films and on television, were viewed in the past), social media has piqued people’s interest in aesthetics. It remains a balance for interested physicians to help keep information about cosmetic procedures presented in a healthy, interesting, professional, and accurate manner, and in a non–time-consuming way.
Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at dermnews@mdedge.com. She had no relevant disclosures.
References
Boen M and Jerdan K. Clin Dermatol. 2022 Jan-Feb;40(1):45-8.
Chen J et al. JAMA Facial Plast Surg. 2019 Sep 1;21(5):361-7.
Chopan M et al. Plast Reconstr Surg. 2019 Apr;143(4):1259-65.
Recently, but I had never heard it before. Not too long afterwards, patients were asking me about it in the office, using the same terminology, and I had several calls about it in one day. When I asked one trusted patient where she’d heard this term, which seemed to be trending, she told me that she had seen it on Instagram, as an ad or a “suggested for you” post.
Whether it’s a different name or term for a cosmetic procedure or laser we use that I’ve never heard before – such as “lip flip” or trap tox (also known as “Barbie Botox”) – many of these trendy terms spread like wildfire on social media. Some of the terms may be marketing tools started and spread by doctors who perform aesthetic procedures, something I don’t recommend as it only creates confusion for patients and practitioners, similar to the confusion consumers face regarding the plethora of over-the-counter skin care options and the marketing terms used for them. Other terms and trends are also started by nonphysician or non–professionally trained providers, sometimes leading to an unsafe or misleading term for an aesthetic procedure.
Over the past few years, several articles about the impact of social media in aesthetics have been published. In one recent paper, published in 2022, Boen and Jerdan noted that 72% of people in the United States use social media, up from 5% of American adults in 2005. In the United States, they note, “YouTube is the most popular platform with 73% of adult users, followed by Facebook (69%), Instagram (37%), SnapChat (24%), and Twitter (22%). Of the sites used daily, Facebook has the most activity (74%), followed by Instagram (64%), SnapChat (63%), YouTube (51%), and Twitter (42%).” They argue that the pros of social media in aesthetic medicine include its use as an educational tool by medical professionals to educate and provide accurate information about cosmetic procedures, and that “providing factual and evidence-based medical information to the public can help to counteract the abundant misinformation that is out there.” The cons include misinformation, no credentialing verification of the provider of the information – essentially anyone can be an “influencer” – as well as the addictive nature of social media for the consumer.
Along the same lines, younger patients tend to rely more on social media in choosing treatments and providers, further perpetuating any anxiety created from misinformation and unrealistic expectations from nonmedical influencers regarding procedures, filters used on photographs, photo editing, etc., in achieving an aesthetic result.
Physicians, particularly fellowship-trained aesthetic and surgical dermatologists, plastic and reconstructive surgeons, oculoplastic surgeons, and ENT facial plastic surgeons, who have the most training, knowledge, and expertise about aesthetic procedures, often have the least amount of time to devote to education via social media, compared with nonmedical influencers. Unless sponsored, they are also not being compensated for using it as an educational tool, except for potential indirect compensation from using it as a marketing tool for themselves and their practices. In contrast, nonmedical influencers often have many followers and time to create content, and in some cases, this is their full-time job.
All in all, most authors agree that social media has been associated with an increased acceptance of cosmetic surgery and procedures. Whether it be a trend seen on social media, or viewing one’s appearance in a filtered or photoediting app, or seeing an image of how another person looks (similar to how people in magazines, films and on television, were viewed in the past), social media has piqued people’s interest in aesthetics. It remains a balance for interested physicians to help keep information about cosmetic procedures presented in a healthy, interesting, professional, and accurate manner, and in a non–time-consuming way.
Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at dermnews@mdedge.com. She had no relevant disclosures.
References
Boen M and Jerdan K. Clin Dermatol. 2022 Jan-Feb;40(1):45-8.
Chen J et al. JAMA Facial Plast Surg. 2019 Sep 1;21(5):361-7.
Chopan M et al. Plast Reconstr Surg. 2019 Apr;143(4):1259-65.
Can skin bleaching lead to cancer?
SINGAPORE –
This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology.
Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”
“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”
Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.
To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.
But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”
His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).
“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”
Misuse leads to complications
The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk.
“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”
In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.
To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).
Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities.
Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye.
An increased risk
But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.
“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed.
If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”
The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.
Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.
Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.
For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”
But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.
To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.
Dr. Faye and Dr. Lupi report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SINGAPORE –
This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology.
Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”
“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”
Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.
To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.
But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”
His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).
“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”
Misuse leads to complications
The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk.
“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”
In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.
To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).
Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities.
Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye.
An increased risk
But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.
“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed.
If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”
The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.
Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.
Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.
For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”
But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.
To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.
Dr. Faye and Dr. Lupi report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SINGAPORE –
This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology.
Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”
“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”
Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.
To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.
But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”
His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).
“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”
Misuse leads to complications
The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk.
“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”
In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.
To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).
Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities.
Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye.
An increased risk
But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.
“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed.
If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”
The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.
Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.
Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.
For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”
But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.
To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.
Dr. Faye and Dr. Lupi report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT WCD 2023
FDA panel deems phenylephrine ineffective
The Nonprescription Drug Advisory Committee discussed the efficacy and pharmacokinetic data for phenylephrine. The committee’s next move is to determine if the drug’s status as Generally Recognized as Safe and Effective should be revoked. This would mean manufacturers would have to come up with new formulations, or products containing the drug would be removed from store shelves. NDAC did not disclose a timeline for assessing GRASE status.
The vote that formally declared phenylephrine ineffective was in line with a review of pharmacology and clinical data presented by the FDA on Sept. 11, which found that the oral bioavailability of the drug is less than 1%, compared with 38%, a number often cited in the literature and based on outdated technology.
A mechanism potentially responsible for inefficacy may be the half-life of phenylephrine.
“The half-life of the parent phenylephrine is much shorter than that of total phenylephrine, suggesting that the duration of action for active parent phenylephrine is far shorter than the monographed dosing interval of every 4 hours and is therefore open to question,” the review states.
The side effects of phenylephrine include headaches, insomnia, and nervousness. At higher doses, it can increase blood pressure.
The review also found that original studies used to support the efficacy of phenylephrine were inconclusive at best and contained potential methodological, statistical, and data integrity issues.
Pseudoephedrine is the only other nonprescription oral nasal decongestant on the retail market but is only available behind the counter due to its use as a potential narcotic.
Manufacturers have used phenylephrine instead of pseudoephedrine in many products due to this limitation.
Revoking the GRASE status of phenylephrine would leave patients without an over-the-counter option.
According to the FDA review, 242 million packages or bottles of phenylephrine products were sold in 2022, resulting in $1.76 billion in sales. A little over 50 million packages of pseudoephedrine were sold that same year, resulting in $542 million in sales.
“I think there’s a huge potential for consumer concern,” Diane B. Ginsburg, PhD, MS, RPh, the pharmacy practice division associate dean for Healthcare Partnerships at The University of Texas at Austin, said during the panel.
She said patients may be confused and concerned about the panel vote, especially those who feel they have benefitted from phenylephrine products. In the event of GRASE removal, she advised reassuring patients that phenylephrine is being pulled from shelves due to inefficacy rather than immediate health risks.
“The real positive here to me is the opportunity from an educational perspective to show consumers the fact that there are a lot more ways to treat” conditions that present with the symptom of congestion, such as rhinitis.
According to the FDA review, “most consumers may simply need instruction on the alternatives, including how to obtain ‘behind-the-counter’ pseudoephedrine or to use alternative treatments, including intranasal decongestants (including intranasal phenylephrine), intranasal steroids, intranasal antihistamines, or intranasal saline products.”
Despite these complications, “there are a number of potential benefits that would be derived by changing the GRASE status of oral phenylephrine.”
These include avoiding unnecessary costs of taking an ineffective drug, potential allergic reactions and side effects, and the risks of patients taking a higher dosage.
A version of this article appeared on Medscape.com.
The Nonprescription Drug Advisory Committee discussed the efficacy and pharmacokinetic data for phenylephrine. The committee’s next move is to determine if the drug’s status as Generally Recognized as Safe and Effective should be revoked. This would mean manufacturers would have to come up with new formulations, or products containing the drug would be removed from store shelves. NDAC did not disclose a timeline for assessing GRASE status.
The vote that formally declared phenylephrine ineffective was in line with a review of pharmacology and clinical data presented by the FDA on Sept. 11, which found that the oral bioavailability of the drug is less than 1%, compared with 38%, a number often cited in the literature and based on outdated technology.
A mechanism potentially responsible for inefficacy may be the half-life of phenylephrine.
“The half-life of the parent phenylephrine is much shorter than that of total phenylephrine, suggesting that the duration of action for active parent phenylephrine is far shorter than the monographed dosing interval of every 4 hours and is therefore open to question,” the review states.
The side effects of phenylephrine include headaches, insomnia, and nervousness. At higher doses, it can increase blood pressure.
The review also found that original studies used to support the efficacy of phenylephrine were inconclusive at best and contained potential methodological, statistical, and data integrity issues.
Pseudoephedrine is the only other nonprescription oral nasal decongestant on the retail market but is only available behind the counter due to its use as a potential narcotic.
Manufacturers have used phenylephrine instead of pseudoephedrine in many products due to this limitation.
Revoking the GRASE status of phenylephrine would leave patients without an over-the-counter option.
According to the FDA review, 242 million packages or bottles of phenylephrine products were sold in 2022, resulting in $1.76 billion in sales. A little over 50 million packages of pseudoephedrine were sold that same year, resulting in $542 million in sales.
“I think there’s a huge potential for consumer concern,” Diane B. Ginsburg, PhD, MS, RPh, the pharmacy practice division associate dean for Healthcare Partnerships at The University of Texas at Austin, said during the panel.
She said patients may be confused and concerned about the panel vote, especially those who feel they have benefitted from phenylephrine products. In the event of GRASE removal, she advised reassuring patients that phenylephrine is being pulled from shelves due to inefficacy rather than immediate health risks.
“The real positive here to me is the opportunity from an educational perspective to show consumers the fact that there are a lot more ways to treat” conditions that present with the symptom of congestion, such as rhinitis.
According to the FDA review, “most consumers may simply need instruction on the alternatives, including how to obtain ‘behind-the-counter’ pseudoephedrine or to use alternative treatments, including intranasal decongestants (including intranasal phenylephrine), intranasal steroids, intranasal antihistamines, or intranasal saline products.”
Despite these complications, “there are a number of potential benefits that would be derived by changing the GRASE status of oral phenylephrine.”
These include avoiding unnecessary costs of taking an ineffective drug, potential allergic reactions and side effects, and the risks of patients taking a higher dosage.
A version of this article appeared on Medscape.com.
The Nonprescription Drug Advisory Committee discussed the efficacy and pharmacokinetic data for phenylephrine. The committee’s next move is to determine if the drug’s status as Generally Recognized as Safe and Effective should be revoked. This would mean manufacturers would have to come up with new formulations, or products containing the drug would be removed from store shelves. NDAC did not disclose a timeline for assessing GRASE status.
The vote that formally declared phenylephrine ineffective was in line with a review of pharmacology and clinical data presented by the FDA on Sept. 11, which found that the oral bioavailability of the drug is less than 1%, compared with 38%, a number often cited in the literature and based on outdated technology.
A mechanism potentially responsible for inefficacy may be the half-life of phenylephrine.
“The half-life of the parent phenylephrine is much shorter than that of total phenylephrine, suggesting that the duration of action for active parent phenylephrine is far shorter than the monographed dosing interval of every 4 hours and is therefore open to question,” the review states.
The side effects of phenylephrine include headaches, insomnia, and nervousness. At higher doses, it can increase blood pressure.
The review also found that original studies used to support the efficacy of phenylephrine were inconclusive at best and contained potential methodological, statistical, and data integrity issues.
Pseudoephedrine is the only other nonprescription oral nasal decongestant on the retail market but is only available behind the counter due to its use as a potential narcotic.
Manufacturers have used phenylephrine instead of pseudoephedrine in many products due to this limitation.
Revoking the GRASE status of phenylephrine would leave patients without an over-the-counter option.
According to the FDA review, 242 million packages or bottles of phenylephrine products were sold in 2022, resulting in $1.76 billion in sales. A little over 50 million packages of pseudoephedrine were sold that same year, resulting in $542 million in sales.
“I think there’s a huge potential for consumer concern,” Diane B. Ginsburg, PhD, MS, RPh, the pharmacy practice division associate dean for Healthcare Partnerships at The University of Texas at Austin, said during the panel.
She said patients may be confused and concerned about the panel vote, especially those who feel they have benefitted from phenylephrine products. In the event of GRASE removal, she advised reassuring patients that phenylephrine is being pulled from shelves due to inefficacy rather than immediate health risks.
“The real positive here to me is the opportunity from an educational perspective to show consumers the fact that there are a lot more ways to treat” conditions that present with the symptom of congestion, such as rhinitis.
According to the FDA review, “most consumers may simply need instruction on the alternatives, including how to obtain ‘behind-the-counter’ pseudoephedrine or to use alternative treatments, including intranasal decongestants (including intranasal phenylephrine), intranasal steroids, intranasal antihistamines, or intranasal saline products.”
Despite these complications, “there are a number of potential benefits that would be derived by changing the GRASE status of oral phenylephrine.”
These include avoiding unnecessary costs of taking an ineffective drug, potential allergic reactions and side effects, and the risks of patients taking a higher dosage.
A version of this article appeared on Medscape.com.
Bad blood: Could brain bleeds be contagious?
This transcript has been edited for clarity.
How do you tell if a condition is caused by an infection?
It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.
Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.
Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.
And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.
We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.
CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.
An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.
Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.
Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.
Of course, to really test that hypothesis, you’d need to know who every blood donor in a country was and every person who received that blood and all their subsequent diagnoses for basically their entire lives. No one has that kind of data, right?
Well, if you’ve been watching this space, you’ll know that a few countries do. Enter Sweden and Denmark, with their national electronic health record that captures all of this information, and much more, on every single person who lives or has lived in those countries since before 1970. Unbelievable.
So that’s exactly what the researchers, led by Jingchen Zhao at Karolinska (Sweden) University, did. They identified roughly 760,000 individuals in Sweden and 330,000 people in Denmark who had received a blood transfusion between 1970 and 2017.
Of course, most of those blood donors – 99% of them, actually – never went on to have any bleeding in the brain. It is a rare thing, fortunately.
But some of the donors did, on average within about 5 years of the time they donated blood. The researchers characterized each donor as either never having a brain bleed, having a single bleed, or having multiple bleeds. The latter is most strongly associated with CAA.
The big question: Would recipients who got blood from individuals who later on had brain bleeds, have brain bleeds themselves?
The answer is yes, though with an asterisk. You can see the results here. The risk of recipients having a brain bleed was lowest if the blood they received was from people who never had a brain bleed, higher if the individual had a single brain bleed, and highest if they got blood from a donor who would go on to have multiple brain bleeds.
All in all, individuals who received blood from someone who would later have multiple hemorrhages were three times more likely to themselves develop bleeds themselves. It’s fairly compelling evidence of a transmissible agent.
Of course, there are some potential confounders to consider here. Whose blood you get is not totally random. If, for example, people with type O blood are just more likely to have brain bleeds, then you could get results like this, as type O tends to donate to type O and both groups would have higher risk after donation. But the authors adjusted for blood type. They also adjusted for number of transfusions, calendar year, age, sex, and indication for transfusion.
Perhaps most compelling, and most clever, is that they used ischemic stroke as a negative control. Would people who received blood from someone who later had an ischemic stroke themselves be more likely to go on to have an ischemic stroke? No signal at all. It does not appear that there is a transmissible agent associated with ischemic stroke – only the brain bleeds.
I know what you’re thinking. What’s the agent? What’s the microbe, or virus, or prion, or toxin? The study gives us no insight there. These nationwide databases are awesome but they can only do so much. Because of the vagaries of medical coding and the difficulty of making the CAA diagnosis, the authors are using brain bleeds as a proxy here; we don’t even know for sure whether these were CAA-associated brain bleeds.
It’s also worth noting that there’s little we can do about this. None of the blood donors in this study had a brain bleed prior to donation; it’s not like we could screen people out of donating in the future. We have no test for whatever this agent is, if it even exists, nor do we have a potential treatment. Fortunately, whatever it is, it is extremely rare.
Still, this paper feels like a shot across the bow. At this point, the probability has shifted strongly away from CAA being a purely random disease and toward it being an infectious one. It may be time to round up some of the unusual suspects.
Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
How do you tell if a condition is caused by an infection?
It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.
Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.
Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.
And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.
We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.
CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.
An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.
Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.
Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.
Of course, to really test that hypothesis, you’d need to know who every blood donor in a country was and every person who received that blood and all their subsequent diagnoses for basically their entire lives. No one has that kind of data, right?
Well, if you’ve been watching this space, you’ll know that a few countries do. Enter Sweden and Denmark, with their national electronic health record that captures all of this information, and much more, on every single person who lives or has lived in those countries since before 1970. Unbelievable.
So that’s exactly what the researchers, led by Jingchen Zhao at Karolinska (Sweden) University, did. They identified roughly 760,000 individuals in Sweden and 330,000 people in Denmark who had received a blood transfusion between 1970 and 2017.
Of course, most of those blood donors – 99% of them, actually – never went on to have any bleeding in the brain. It is a rare thing, fortunately.
But some of the donors did, on average within about 5 years of the time they donated blood. The researchers characterized each donor as either never having a brain bleed, having a single bleed, or having multiple bleeds. The latter is most strongly associated with CAA.
The big question: Would recipients who got blood from individuals who later on had brain bleeds, have brain bleeds themselves?
The answer is yes, though with an asterisk. You can see the results here. The risk of recipients having a brain bleed was lowest if the blood they received was from people who never had a brain bleed, higher if the individual had a single brain bleed, and highest if they got blood from a donor who would go on to have multiple brain bleeds.
All in all, individuals who received blood from someone who would later have multiple hemorrhages were three times more likely to themselves develop bleeds themselves. It’s fairly compelling evidence of a transmissible agent.
Of course, there are some potential confounders to consider here. Whose blood you get is not totally random. If, for example, people with type O blood are just more likely to have brain bleeds, then you could get results like this, as type O tends to donate to type O and both groups would have higher risk after donation. But the authors adjusted for blood type. They also adjusted for number of transfusions, calendar year, age, sex, and indication for transfusion.
Perhaps most compelling, and most clever, is that they used ischemic stroke as a negative control. Would people who received blood from someone who later had an ischemic stroke themselves be more likely to go on to have an ischemic stroke? No signal at all. It does not appear that there is a transmissible agent associated with ischemic stroke – only the brain bleeds.
I know what you’re thinking. What’s the agent? What’s the microbe, or virus, or prion, or toxin? The study gives us no insight there. These nationwide databases are awesome but they can only do so much. Because of the vagaries of medical coding and the difficulty of making the CAA diagnosis, the authors are using brain bleeds as a proxy here; we don’t even know for sure whether these were CAA-associated brain bleeds.
It’s also worth noting that there’s little we can do about this. None of the blood donors in this study had a brain bleed prior to donation; it’s not like we could screen people out of donating in the future. We have no test for whatever this agent is, if it even exists, nor do we have a potential treatment. Fortunately, whatever it is, it is extremely rare.
Still, this paper feels like a shot across the bow. At this point, the probability has shifted strongly away from CAA being a purely random disease and toward it being an infectious one. It may be time to round up some of the unusual suspects.
Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
How do you tell if a condition is caused by an infection?
It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.
Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.
Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.
And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.
We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.
CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.
An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.
Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.
Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.
Of course, to really test that hypothesis, you’d need to know who every blood donor in a country was and every person who received that blood and all their subsequent diagnoses for basically their entire lives. No one has that kind of data, right?
Well, if you’ve been watching this space, you’ll know that a few countries do. Enter Sweden and Denmark, with their national electronic health record that captures all of this information, and much more, on every single person who lives or has lived in those countries since before 1970. Unbelievable.
So that’s exactly what the researchers, led by Jingchen Zhao at Karolinska (Sweden) University, did. They identified roughly 760,000 individuals in Sweden and 330,000 people in Denmark who had received a blood transfusion between 1970 and 2017.
Of course, most of those blood donors – 99% of them, actually – never went on to have any bleeding in the brain. It is a rare thing, fortunately.
But some of the donors did, on average within about 5 years of the time they donated blood. The researchers characterized each donor as either never having a brain bleed, having a single bleed, or having multiple bleeds. The latter is most strongly associated with CAA.
The big question: Would recipients who got blood from individuals who later on had brain bleeds, have brain bleeds themselves?
The answer is yes, though with an asterisk. You can see the results here. The risk of recipients having a brain bleed was lowest if the blood they received was from people who never had a brain bleed, higher if the individual had a single brain bleed, and highest if they got blood from a donor who would go on to have multiple brain bleeds.
All in all, individuals who received blood from someone who would later have multiple hemorrhages were three times more likely to themselves develop bleeds themselves. It’s fairly compelling evidence of a transmissible agent.
Of course, there are some potential confounders to consider here. Whose blood you get is not totally random. If, for example, people with type O blood are just more likely to have brain bleeds, then you could get results like this, as type O tends to donate to type O and both groups would have higher risk after donation. But the authors adjusted for blood type. They also adjusted for number of transfusions, calendar year, age, sex, and indication for transfusion.
Perhaps most compelling, and most clever, is that they used ischemic stroke as a negative control. Would people who received blood from someone who later had an ischemic stroke themselves be more likely to go on to have an ischemic stroke? No signal at all. It does not appear that there is a transmissible agent associated with ischemic stroke – only the brain bleeds.
I know what you’re thinking. What’s the agent? What’s the microbe, or virus, or prion, or toxin? The study gives us no insight there. These nationwide databases are awesome but they can only do so much. Because of the vagaries of medical coding and the difficulty of making the CAA diagnosis, the authors are using brain bleeds as a proxy here; we don’t even know for sure whether these were CAA-associated brain bleeds.
It’s also worth noting that there’s little we can do about this. None of the blood donors in this study had a brain bleed prior to donation; it’s not like we could screen people out of donating in the future. We have no test for whatever this agent is, if it even exists, nor do we have a potential treatment. Fortunately, whatever it is, it is extremely rare.
Still, this paper feels like a shot across the bow. At this point, the probability has shifted strongly away from CAA being a purely random disease and toward it being an infectious one. It may be time to round up some of the unusual suspects.
Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Stress, insomnia tied to increased AFib risk for older women
TOPLINE:
Eight psychosocial factors, grouped into two distinct clusters, are significantly associated with risk for atrial fibrillation in postmenopausal women, with insomnia and stressful life events (SLEs) being the most strongly associated with AFib, a large new study has found.
METHODOLOGY:
- In addition to traditional risk factors such as obesity, advanced age, ethnicity, smoking, alcohol, hypertension, diabetes, coronary artery disease, heart failure, and emotional and psychological distress may also affect AFib.
- The study included 83,736 postmenopausal women in the Women’s Health Initiative (mean age, 63.9 years; 88.1% White) who did not have AFib at baseline.
- From questionnaires, researchers collected information on psychosocial stressors and used hierarchical cluster analysis to identify patterns of psychosocial predictors.
- They separated these clusters into quartiles, identified associations between psychosocial exposure variables, and adjusted for traditional risk factors.
- Over an average follow-up of 10.5 years, 23,954 participants (28.6%) developed incident AFib.
TAKEAWAY:
- The analysis generated two clusters of distinct psychosocial variables that were significantly associated with AFib: the Stress Cluster, including SLEs, depressive symptoms, and insomnia; and the Strain Cluster, including three personality traits: optimism, cynical hostility, and emotional expressiveness; and two social measures: social support, and social strain.
- Those in the highest quartiles of both the Stress Cluster and the Strain Cluster had greater rates of AFib, compared with those in the lowest quartiles.
- In a final model, the association between SLEs (hazard ratio, 1.02; 95% confidence interval, 1.01-1.04) and insomnia (HR, 1.04; 95% CI, 1.03-1.06) were most strongly linked to increased incidence of AFib, and a sensitivity analysis using snoring as a surrogate marker for sleep apnea didn’t change this outcome, supporting the independent effect of insomnia on AFib.
- In subgroup analyses, the Stress Cluster had a stronger association with AFib incidence in younger (50-69 years) versus older women (70-79 years), and in non-Hispanic White and Asian women versus Hispanic and non-Hispanic Black women.
IN PRACTICE:
The results support the hypothesis that psychosocial predictors account for additional risk for AFib “above and beyond” traditional risk factors, the authors wrote. Identifying and addressing sex-specific, modifiable risk factors, including insomnia, “may help reduce the burden of AF[ib] in aging women.”
SOURCE:
The study was conducted by Susan X. Zhao, MD, division of cardiology, department of medicine, Santa Clara Valley Medical Center, San Jose, Calif., and colleagues. It was published online in the Journal of the American Heart Association.
LIMITATIONS:
The psychometric questionnaires were administered only at study entry, but psychosocial variables may change over time. Data on sleep apnea and other sleep disorders, which may confound the relationship between insomnia and AFib, were not available, and although the study included a sensitivity analysis controlling for snoring, this is an imperfect surrogate for sleep apnea. Generalizability to other demographic, racial, and ethnic groups is limited.
DISCLOSURES:
The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The authors have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Eight psychosocial factors, grouped into two distinct clusters, are significantly associated with risk for atrial fibrillation in postmenopausal women, with insomnia and stressful life events (SLEs) being the most strongly associated with AFib, a large new study has found.
METHODOLOGY:
- In addition to traditional risk factors such as obesity, advanced age, ethnicity, smoking, alcohol, hypertension, diabetes, coronary artery disease, heart failure, and emotional and psychological distress may also affect AFib.
- The study included 83,736 postmenopausal women in the Women’s Health Initiative (mean age, 63.9 years; 88.1% White) who did not have AFib at baseline.
- From questionnaires, researchers collected information on psychosocial stressors and used hierarchical cluster analysis to identify patterns of psychosocial predictors.
- They separated these clusters into quartiles, identified associations between psychosocial exposure variables, and adjusted for traditional risk factors.
- Over an average follow-up of 10.5 years, 23,954 participants (28.6%) developed incident AFib.
TAKEAWAY:
- The analysis generated two clusters of distinct psychosocial variables that were significantly associated with AFib: the Stress Cluster, including SLEs, depressive symptoms, and insomnia; and the Strain Cluster, including three personality traits: optimism, cynical hostility, and emotional expressiveness; and two social measures: social support, and social strain.
- Those in the highest quartiles of both the Stress Cluster and the Strain Cluster had greater rates of AFib, compared with those in the lowest quartiles.
- In a final model, the association between SLEs (hazard ratio, 1.02; 95% confidence interval, 1.01-1.04) and insomnia (HR, 1.04; 95% CI, 1.03-1.06) were most strongly linked to increased incidence of AFib, and a sensitivity analysis using snoring as a surrogate marker for sleep apnea didn’t change this outcome, supporting the independent effect of insomnia on AFib.
- In subgroup analyses, the Stress Cluster had a stronger association with AFib incidence in younger (50-69 years) versus older women (70-79 years), and in non-Hispanic White and Asian women versus Hispanic and non-Hispanic Black women.
IN PRACTICE:
The results support the hypothesis that psychosocial predictors account for additional risk for AFib “above and beyond” traditional risk factors, the authors wrote. Identifying and addressing sex-specific, modifiable risk factors, including insomnia, “may help reduce the burden of AF[ib] in aging women.”
SOURCE:
The study was conducted by Susan X. Zhao, MD, division of cardiology, department of medicine, Santa Clara Valley Medical Center, San Jose, Calif., and colleagues. It was published online in the Journal of the American Heart Association.
LIMITATIONS:
The psychometric questionnaires were administered only at study entry, but psychosocial variables may change over time. Data on sleep apnea and other sleep disorders, which may confound the relationship between insomnia and AFib, were not available, and although the study included a sensitivity analysis controlling for snoring, this is an imperfect surrogate for sleep apnea. Generalizability to other demographic, racial, and ethnic groups is limited.
DISCLOSURES:
The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The authors have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Eight psychosocial factors, grouped into two distinct clusters, are significantly associated with risk for atrial fibrillation in postmenopausal women, with insomnia and stressful life events (SLEs) being the most strongly associated with AFib, a large new study has found.
METHODOLOGY:
- In addition to traditional risk factors such as obesity, advanced age, ethnicity, smoking, alcohol, hypertension, diabetes, coronary artery disease, heart failure, and emotional and psychological distress may also affect AFib.
- The study included 83,736 postmenopausal women in the Women’s Health Initiative (mean age, 63.9 years; 88.1% White) who did not have AFib at baseline.
- From questionnaires, researchers collected information on psychosocial stressors and used hierarchical cluster analysis to identify patterns of psychosocial predictors.
- They separated these clusters into quartiles, identified associations between psychosocial exposure variables, and adjusted for traditional risk factors.
- Over an average follow-up of 10.5 years, 23,954 participants (28.6%) developed incident AFib.
TAKEAWAY:
- The analysis generated two clusters of distinct psychosocial variables that were significantly associated with AFib: the Stress Cluster, including SLEs, depressive symptoms, and insomnia; and the Strain Cluster, including three personality traits: optimism, cynical hostility, and emotional expressiveness; and two social measures: social support, and social strain.
- Those in the highest quartiles of both the Stress Cluster and the Strain Cluster had greater rates of AFib, compared with those in the lowest quartiles.
- In a final model, the association between SLEs (hazard ratio, 1.02; 95% confidence interval, 1.01-1.04) and insomnia (HR, 1.04; 95% CI, 1.03-1.06) were most strongly linked to increased incidence of AFib, and a sensitivity analysis using snoring as a surrogate marker for sleep apnea didn’t change this outcome, supporting the independent effect of insomnia on AFib.
- In subgroup analyses, the Stress Cluster had a stronger association with AFib incidence in younger (50-69 years) versus older women (70-79 years), and in non-Hispanic White and Asian women versus Hispanic and non-Hispanic Black women.
IN PRACTICE:
The results support the hypothesis that psychosocial predictors account for additional risk for AFib “above and beyond” traditional risk factors, the authors wrote. Identifying and addressing sex-specific, modifiable risk factors, including insomnia, “may help reduce the burden of AF[ib] in aging women.”
SOURCE:
The study was conducted by Susan X. Zhao, MD, division of cardiology, department of medicine, Santa Clara Valley Medical Center, San Jose, Calif., and colleagues. It was published online in the Journal of the American Heart Association.
LIMITATIONS:
The psychometric questionnaires were administered only at study entry, but psychosocial variables may change over time. Data on sleep apnea and other sleep disorders, which may confound the relationship between insomnia and AFib, were not available, and although the study included a sensitivity analysis controlling for snoring, this is an imperfect surrogate for sleep apnea. Generalizability to other demographic, racial, and ethnic groups is limited.
DISCLOSURES:
The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The authors have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM JOURNAL OF THE AMERICAN HEART ASSOCIATION
Disenfranchised grief: What it looks like, where it goes
What happens to grief when those around you don’t understand it? Where does it go? How do you process it?
Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.
Suzanne Cole, MD: ‘I didn’t feel the right to grieve’
During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.
Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.
But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.
To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
Don S. Dizon, MD: Working through tragedy
As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.
But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.
Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.
By the time help arrived, the patient was blue.
He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.
As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
A space for grieving: The Schwartz Center Rounds
Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.
Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.
More and more, though, we are being given opportunities to reflect on these sad moments.
The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.
During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.
As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.
Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.
Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.
As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.
We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.
Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.
A version of this article first appeared on Medscape.com.
What happens to grief when those around you don’t understand it? Where does it go? How do you process it?
Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.
Suzanne Cole, MD: ‘I didn’t feel the right to grieve’
During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.
Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.
But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.
To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
Don S. Dizon, MD: Working through tragedy
As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.
But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.
Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.
By the time help arrived, the patient was blue.
He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.
As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
A space for grieving: The Schwartz Center Rounds
Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.
Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.
More and more, though, we are being given opportunities to reflect on these sad moments.
The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.
During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.
As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.
Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.
Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.
As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.
We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.
Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.
A version of this article first appeared on Medscape.com.
What happens to grief when those around you don’t understand it? Where does it go? How do you process it?
Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.
Suzanne Cole, MD: ‘I didn’t feel the right to grieve’
During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.
Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.
But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.
To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
Don S. Dizon, MD: Working through tragedy
As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.
But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.
Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.
By the time help arrived, the patient was blue.
He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.
As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
A space for grieving: The Schwartz Center Rounds
Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.
Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.
More and more, though, we are being given opportunities to reflect on these sad moments.
The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.
During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.
As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.
Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.
Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.
As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.
We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.
Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.
A version of this article first appeared on Medscape.com.
24-year-old woman • large joint arthralgias • history of type 1 diabetes, seizures, migraines • Dx?
THE CASE
A 24-year-old woman with a history of type 1 diabetes, seizure disorder, and migraines presented to a rural Federally Qualified Health Center (FQHC) with progressive and severe symmetric large joint arthralgias of several weeks’ duration. The patient’s existing medications included etonogestrel 68 mg subdermal implant, levetiracetam 1500 mg bid, insulin glargine 26 units subcutaneously nightly, and insulin lispro 20 units subcutaneously tid (before meals).
An examination revealed symmetrically edematous elbows, wrists, and fingers. Subsequent serologic analyses and a telemedicine consultation with a rheumatologist confirmed a diagnosis of rheumatoid arthritis (RA). The patient’s lab work was positive for antinuclear antibody titers (1:40), rheumatoid factor (513 IU/mL), and anticyclic citrullinated peptide antibodies (248 units/mL). Treatment was started with prednisone 60 mg PO daily, methotrexate 20 mg PO weekly, and hydroxychloroquine 400 mg PO daily. (The benefits of prednisone in treating this patient’s severe arthralgias outweighed concerns over its use in a patient with diabetes.)
After 2 months of receiving RA therapy, the patient underwent further work-up to assess its effectiveness
Upon receiving a diagnosis of active hepatitis C, the patient acknowledged that she’d had unprotected heterosexual intercourse and shared used insulin syringes with friends.
THE DIAGNOSIS
Consideration was given to a diagnosis of HCV arthropathy, which can present as an RA-like arthritis in HCV-infected individuals, in the differential diagnosis.1 A cohort study found HCV-associated arthropathy occurred in 6.8% of those with chronic HCV infection.2
However, the symmetrical involvement of shoulders and knees as the patient’s primary arthralgias, and a rheumatologic work-up showing the presence of anticyclic citrullinated peptide antibody levels, confirmed the diagnosis of RA with coexisting HCV.
DISCUSSION
Delivering interdisciplinary care in a rural area
Although evidence-based guidelines and online HCV Treatment Path programs guided the initial evaluation of potential treatments for this patient, her multiple comorbidities prompted us to seek out additional, interdisciplinary advice through a resource for underserved communities called Project Extension for Community Healthcare Outcomes (ECHO; see “What is Project ECHO?3,4”). The patient’s case was presented virtually, without identifying information, to a multidisciplinary HCV team. Two treatment options were suggested:
- sofosbuvir/velpatasvir (400 mg/100 mg) for 12 weeks or
- glecaprevir/pibrentasvir (100 mg/40 mg) for 8 weeks.
SIDEBAR
What is Project ECHO?
Project Extension for Community Healthcare Outcomes (ECHO) began as an avenue to connect hepatitis C virus (HCV) treatment experts to providers in underserved communities within New Mexico. Specialists can offer their clinical guidance to community clinicians without seeing the patient themselves.3 Project ECHO now has expanded to connect community clinicians across the United States and globally to specialists who treat other chronic conditions.4 More information about Project ECHO can be found at hsc.unm.edu/echo.
Both are evidence-based and recommended treatment options according to the HCV treatment guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.5
In most patients with HCV, treatment is guided by a number of factors, including pill burden, access to care, duration of therapy, drug interactions, and patient-specific needs. After analyzing all aspects of this patient’s case, 2 major concerns guided our shared decision-making process on treatment.
The best treatment is what works for the patient
Owing to the patient’s multiple comorbidities and prescribed medications for chronic diseases, concerns about possible medication interactions with the HCV treatment options were a factor in her HCV treatment plan. Additionally, the patient had significant social determinants of health barriers that made continued treatment and follow-up challenging.
The potential interaction of HCV infection treatment with the patient’s current methotrexate therapy for her RA was a primary concern. To determine the risk for interactions, the team used the University of Liverpool HEP/HIV Drug Interactions Checker, which helps identify possible interactions with these disease-specific medication therapies.6
Both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir have a potential interaction with methotrexate and are driven by a similar mechanism. Methotrexate is a substrate of the Breast Cancer Resistance Protein efflux transporter (BCRP), and the components of both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir are inhibitors of BCRP.7 The inhibition of this efflux transporter can lead to an increased concentration of methotrexate, increasing the risk for methotrexate toxicity.7
Since no quantitative data exist regarding the degree of inhibition that these HCV drugs exert on BCRP, the team considered sofosbuvir/velpatasvir and glecaprevir/pibrentasvir to have equal risk with regard to potential for drug interactions.
The patient’s barriers to treatment were another area of concern that directed our therapy decision. The patient had multiple barriers, including poor access to health care because of transportation issues, multiple children requiring care, a variety of chronic diseases, and other life stressors. Shared decision-making ensured our patient’s autonomy in choosing a specific treatment.
The patient’s social situation and preference narrowed the team’s basis for medication choice primarily down to the duration of therapy: 8 weeks of glecaprevir/pibrentasvir vs 12 weeks of sofosbuvir/velpatasvir. The patient mentioned multiple transportation challenges for follow-up visits to the clinic and therefore wanted to utilize the shorter treatment duration. Follow-up is needed every 4 weeks, so the patient was able to go from 3 to 2 visits.
For problems, there are solutions. Following careful consideration of these patient-specific factors and preferences, the team decided to begin therapy with glecaprevir/pibrentasvir. The patient worked with an outreach specialist at the FQHC to coordinate care and complete paperwork for the Project ECHO consultation. The outreach specialist also assisted the patient in completing paperwork for the Patient Assistance Program for HCV treatment. Because the patient is being cared for at an FQHC, the clinic’s in-house pharmacy was able to utilize the 340B Federal Drug Pricing Program, which makes otherwise out-of-reach medicines affordable for patients such as ours.
Our patient has had no issues with treatment adherence, adverse effects, or follow-up appointments. The patient’s RA symptoms have improved significantly without any discernable worsening of her HCV infection.
THE TAKEAWAY
This case shines a light on the multiple challenges (clinical, geographic, and financial) that could have come between our patient and proper treatment—but ultimately, did not. The Project ECHO model of care remains a viable way to provide patients who live in rural and underserved communities and who have active HCV and other underlying chronic conditions with interdisciplinary care that can improve health outcomes.
1. Kemmer NM, Sherman KE. Hepatitis C-related arthropathy: diagnostic and treatment considerations. J Musculoskelet Med. 2010;27:351-354.
2. Ferucci ED, Choromanski TL, Varney DT, et al. Prevalence and correlates of hepatitis C virus-associated inflammatory arthritis in a population-based cohort. Semin Arthritis Rheum. 2017;47:445-450. doi: 10.1016/j.semarthrit.2017.04.004
3. Arora S, Kalishman S, Thornton K, et al. Expanding access to hepatitis C virus treatment--Extension for Community Healthcare Outcomes (ECHO) project: disruptive innovation in specialty care. Hepatology. 2010;52:1124-1133. doi: 10.1002/hep.23802
4. Blecker S, Paul MM, Jones S, et al. A Project ECHO and community health worker intervention for patients with diabetes. Am J Med. 2021;S0002-9343(21)00811-1. doi: 10.1016/j.amjmed.2021.12.002
5. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Accessed June 16, 2023. www.hcvguidelines.org
6. HEP/HIV Drug Interactions Checker University of Liverpool. Interaction Report. Published 2022. Accessed June 26, 2023. www.hep-druginteractions.org/downloads/ajd45jg-4er5-67oy-ur43- 009ert.pdf?interaction_ids%5B%5D=88015&interaction_ids%5B%5D=91366
7. Hong J, Wright RC, Partovi N, et al. Review of clinically relevant drug interactions with next generation hepatitis C direct-acting antiviral agents. J Clin Transl Hepatol. 2020;8:322-335. doi: 10.14218/JCTH.2020.00034
THE CASE
A 24-year-old woman with a history of type 1 diabetes, seizure disorder, and migraines presented to a rural Federally Qualified Health Center (FQHC) with progressive and severe symmetric large joint arthralgias of several weeks’ duration. The patient’s existing medications included etonogestrel 68 mg subdermal implant, levetiracetam 1500 mg bid, insulin glargine 26 units subcutaneously nightly, and insulin lispro 20 units subcutaneously tid (before meals).
An examination revealed symmetrically edematous elbows, wrists, and fingers. Subsequent serologic analyses and a telemedicine consultation with a rheumatologist confirmed a diagnosis of rheumatoid arthritis (RA). The patient’s lab work was positive for antinuclear antibody titers (1:40), rheumatoid factor (513 IU/mL), and anticyclic citrullinated peptide antibodies (248 units/mL). Treatment was started with prednisone 60 mg PO daily, methotrexate 20 mg PO weekly, and hydroxychloroquine 400 mg PO daily. (The benefits of prednisone in treating this patient’s severe arthralgias outweighed concerns over its use in a patient with diabetes.)
After 2 months of receiving RA therapy, the patient underwent further work-up to assess its effectiveness
Upon receiving a diagnosis of active hepatitis C, the patient acknowledged that she’d had unprotected heterosexual intercourse and shared used insulin syringes with friends.
THE DIAGNOSIS
Consideration was given to a diagnosis of HCV arthropathy, which can present as an RA-like arthritis in HCV-infected individuals, in the differential diagnosis.1 A cohort study found HCV-associated arthropathy occurred in 6.8% of those with chronic HCV infection.2
However, the symmetrical involvement of shoulders and knees as the patient’s primary arthralgias, and a rheumatologic work-up showing the presence of anticyclic citrullinated peptide antibody levels, confirmed the diagnosis of RA with coexisting HCV.
DISCUSSION
Delivering interdisciplinary care in a rural area
Although evidence-based guidelines and online HCV Treatment Path programs guided the initial evaluation of potential treatments for this patient, her multiple comorbidities prompted us to seek out additional, interdisciplinary advice through a resource for underserved communities called Project Extension for Community Healthcare Outcomes (ECHO; see “What is Project ECHO?3,4”). The patient’s case was presented virtually, without identifying information, to a multidisciplinary HCV team. Two treatment options were suggested:
- sofosbuvir/velpatasvir (400 mg/100 mg) for 12 weeks or
- glecaprevir/pibrentasvir (100 mg/40 mg) for 8 weeks.
SIDEBAR
What is Project ECHO?
Project Extension for Community Healthcare Outcomes (ECHO) began as an avenue to connect hepatitis C virus (HCV) treatment experts to providers in underserved communities within New Mexico. Specialists can offer their clinical guidance to community clinicians without seeing the patient themselves.3 Project ECHO now has expanded to connect community clinicians across the United States and globally to specialists who treat other chronic conditions.4 More information about Project ECHO can be found at hsc.unm.edu/echo.
Both are evidence-based and recommended treatment options according to the HCV treatment guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.5
In most patients with HCV, treatment is guided by a number of factors, including pill burden, access to care, duration of therapy, drug interactions, and patient-specific needs. After analyzing all aspects of this patient’s case, 2 major concerns guided our shared decision-making process on treatment.
The best treatment is what works for the patient
Owing to the patient’s multiple comorbidities and prescribed medications for chronic diseases, concerns about possible medication interactions with the HCV treatment options were a factor in her HCV treatment plan. Additionally, the patient had significant social determinants of health barriers that made continued treatment and follow-up challenging.
The potential interaction of HCV infection treatment with the patient’s current methotrexate therapy for her RA was a primary concern. To determine the risk for interactions, the team used the University of Liverpool HEP/HIV Drug Interactions Checker, which helps identify possible interactions with these disease-specific medication therapies.6
Both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir have a potential interaction with methotrexate and are driven by a similar mechanism. Methotrexate is a substrate of the Breast Cancer Resistance Protein efflux transporter (BCRP), and the components of both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir are inhibitors of BCRP.7 The inhibition of this efflux transporter can lead to an increased concentration of methotrexate, increasing the risk for methotrexate toxicity.7
Since no quantitative data exist regarding the degree of inhibition that these HCV drugs exert on BCRP, the team considered sofosbuvir/velpatasvir and glecaprevir/pibrentasvir to have equal risk with regard to potential for drug interactions.
The patient’s barriers to treatment were another area of concern that directed our therapy decision. The patient had multiple barriers, including poor access to health care because of transportation issues, multiple children requiring care, a variety of chronic diseases, and other life stressors. Shared decision-making ensured our patient’s autonomy in choosing a specific treatment.
The patient’s social situation and preference narrowed the team’s basis for medication choice primarily down to the duration of therapy: 8 weeks of glecaprevir/pibrentasvir vs 12 weeks of sofosbuvir/velpatasvir. The patient mentioned multiple transportation challenges for follow-up visits to the clinic and therefore wanted to utilize the shorter treatment duration. Follow-up is needed every 4 weeks, so the patient was able to go from 3 to 2 visits.
For problems, there are solutions. Following careful consideration of these patient-specific factors and preferences, the team decided to begin therapy with glecaprevir/pibrentasvir. The patient worked with an outreach specialist at the FQHC to coordinate care and complete paperwork for the Project ECHO consultation. The outreach specialist also assisted the patient in completing paperwork for the Patient Assistance Program for HCV treatment. Because the patient is being cared for at an FQHC, the clinic’s in-house pharmacy was able to utilize the 340B Federal Drug Pricing Program, which makes otherwise out-of-reach medicines affordable for patients such as ours.
Our patient has had no issues with treatment adherence, adverse effects, or follow-up appointments. The patient’s RA symptoms have improved significantly without any discernable worsening of her HCV infection.
THE TAKEAWAY
This case shines a light on the multiple challenges (clinical, geographic, and financial) that could have come between our patient and proper treatment—but ultimately, did not. The Project ECHO model of care remains a viable way to provide patients who live in rural and underserved communities and who have active HCV and other underlying chronic conditions with interdisciplinary care that can improve health outcomes.
THE CASE
A 24-year-old woman with a history of type 1 diabetes, seizure disorder, and migraines presented to a rural Federally Qualified Health Center (FQHC) with progressive and severe symmetric large joint arthralgias of several weeks’ duration. The patient’s existing medications included etonogestrel 68 mg subdermal implant, levetiracetam 1500 mg bid, insulin glargine 26 units subcutaneously nightly, and insulin lispro 20 units subcutaneously tid (before meals).
An examination revealed symmetrically edematous elbows, wrists, and fingers. Subsequent serologic analyses and a telemedicine consultation with a rheumatologist confirmed a diagnosis of rheumatoid arthritis (RA). The patient’s lab work was positive for antinuclear antibody titers (1:40), rheumatoid factor (513 IU/mL), and anticyclic citrullinated peptide antibodies (248 units/mL). Treatment was started with prednisone 60 mg PO daily, methotrexate 20 mg PO weekly, and hydroxychloroquine 400 mg PO daily. (The benefits of prednisone in treating this patient’s severe arthralgias outweighed concerns over its use in a patient with diabetes.)
After 2 months of receiving RA therapy, the patient underwent further work-up to assess its effectiveness
Upon receiving a diagnosis of active hepatitis C, the patient acknowledged that she’d had unprotected heterosexual intercourse and shared used insulin syringes with friends.
THE DIAGNOSIS
Consideration was given to a diagnosis of HCV arthropathy, which can present as an RA-like arthritis in HCV-infected individuals, in the differential diagnosis.1 A cohort study found HCV-associated arthropathy occurred in 6.8% of those with chronic HCV infection.2
However, the symmetrical involvement of shoulders and knees as the patient’s primary arthralgias, and a rheumatologic work-up showing the presence of anticyclic citrullinated peptide antibody levels, confirmed the diagnosis of RA with coexisting HCV.
DISCUSSION
Delivering interdisciplinary care in a rural area
Although evidence-based guidelines and online HCV Treatment Path programs guided the initial evaluation of potential treatments for this patient, her multiple comorbidities prompted us to seek out additional, interdisciplinary advice through a resource for underserved communities called Project Extension for Community Healthcare Outcomes (ECHO; see “What is Project ECHO?3,4”). The patient’s case was presented virtually, without identifying information, to a multidisciplinary HCV team. Two treatment options were suggested:
- sofosbuvir/velpatasvir (400 mg/100 mg) for 12 weeks or
- glecaprevir/pibrentasvir (100 mg/40 mg) for 8 weeks.
SIDEBAR
What is Project ECHO?
Project Extension for Community Healthcare Outcomes (ECHO) began as an avenue to connect hepatitis C virus (HCV) treatment experts to providers in underserved communities within New Mexico. Specialists can offer their clinical guidance to community clinicians without seeing the patient themselves.3 Project ECHO now has expanded to connect community clinicians across the United States and globally to specialists who treat other chronic conditions.4 More information about Project ECHO can be found at hsc.unm.edu/echo.
Both are evidence-based and recommended treatment options according to the HCV treatment guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.5
In most patients with HCV, treatment is guided by a number of factors, including pill burden, access to care, duration of therapy, drug interactions, and patient-specific needs. After analyzing all aspects of this patient’s case, 2 major concerns guided our shared decision-making process on treatment.
The best treatment is what works for the patient
Owing to the patient’s multiple comorbidities and prescribed medications for chronic diseases, concerns about possible medication interactions with the HCV treatment options were a factor in her HCV treatment plan. Additionally, the patient had significant social determinants of health barriers that made continued treatment and follow-up challenging.
The potential interaction of HCV infection treatment with the patient’s current methotrexate therapy for her RA was a primary concern. To determine the risk for interactions, the team used the University of Liverpool HEP/HIV Drug Interactions Checker, which helps identify possible interactions with these disease-specific medication therapies.6
Both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir have a potential interaction with methotrexate and are driven by a similar mechanism. Methotrexate is a substrate of the Breast Cancer Resistance Protein efflux transporter (BCRP), and the components of both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir are inhibitors of BCRP.7 The inhibition of this efflux transporter can lead to an increased concentration of methotrexate, increasing the risk for methotrexate toxicity.7
Since no quantitative data exist regarding the degree of inhibition that these HCV drugs exert on BCRP, the team considered sofosbuvir/velpatasvir and glecaprevir/pibrentasvir to have equal risk with regard to potential for drug interactions.
The patient’s barriers to treatment were another area of concern that directed our therapy decision. The patient had multiple barriers, including poor access to health care because of transportation issues, multiple children requiring care, a variety of chronic diseases, and other life stressors. Shared decision-making ensured our patient’s autonomy in choosing a specific treatment.
The patient’s social situation and preference narrowed the team’s basis for medication choice primarily down to the duration of therapy: 8 weeks of glecaprevir/pibrentasvir vs 12 weeks of sofosbuvir/velpatasvir. The patient mentioned multiple transportation challenges for follow-up visits to the clinic and therefore wanted to utilize the shorter treatment duration. Follow-up is needed every 4 weeks, so the patient was able to go from 3 to 2 visits.
For problems, there are solutions. Following careful consideration of these patient-specific factors and preferences, the team decided to begin therapy with glecaprevir/pibrentasvir. The patient worked with an outreach specialist at the FQHC to coordinate care and complete paperwork for the Project ECHO consultation. The outreach specialist also assisted the patient in completing paperwork for the Patient Assistance Program for HCV treatment. Because the patient is being cared for at an FQHC, the clinic’s in-house pharmacy was able to utilize the 340B Federal Drug Pricing Program, which makes otherwise out-of-reach medicines affordable for patients such as ours.
Our patient has had no issues with treatment adherence, adverse effects, or follow-up appointments. The patient’s RA symptoms have improved significantly without any discernable worsening of her HCV infection.
THE TAKEAWAY
This case shines a light on the multiple challenges (clinical, geographic, and financial) that could have come between our patient and proper treatment—but ultimately, did not. The Project ECHO model of care remains a viable way to provide patients who live in rural and underserved communities and who have active HCV and other underlying chronic conditions with interdisciplinary care that can improve health outcomes.
1. Kemmer NM, Sherman KE. Hepatitis C-related arthropathy: diagnostic and treatment considerations. J Musculoskelet Med. 2010;27:351-354.
2. Ferucci ED, Choromanski TL, Varney DT, et al. Prevalence and correlates of hepatitis C virus-associated inflammatory arthritis in a population-based cohort. Semin Arthritis Rheum. 2017;47:445-450. doi: 10.1016/j.semarthrit.2017.04.004
3. Arora S, Kalishman S, Thornton K, et al. Expanding access to hepatitis C virus treatment--Extension for Community Healthcare Outcomes (ECHO) project: disruptive innovation in specialty care. Hepatology. 2010;52:1124-1133. doi: 10.1002/hep.23802
4. Blecker S, Paul MM, Jones S, et al. A Project ECHO and community health worker intervention for patients with diabetes. Am J Med. 2021;S0002-9343(21)00811-1. doi: 10.1016/j.amjmed.2021.12.002
5. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Accessed June 16, 2023. www.hcvguidelines.org
6. HEP/HIV Drug Interactions Checker University of Liverpool. Interaction Report. Published 2022. Accessed June 26, 2023. www.hep-druginteractions.org/downloads/ajd45jg-4er5-67oy-ur43- 009ert.pdf?interaction_ids%5B%5D=88015&interaction_ids%5B%5D=91366
7. Hong J, Wright RC, Partovi N, et al. Review of clinically relevant drug interactions with next generation hepatitis C direct-acting antiviral agents. J Clin Transl Hepatol. 2020;8:322-335. doi: 10.14218/JCTH.2020.00034
1. Kemmer NM, Sherman KE. Hepatitis C-related arthropathy: diagnostic and treatment considerations. J Musculoskelet Med. 2010;27:351-354.
2. Ferucci ED, Choromanski TL, Varney DT, et al. Prevalence and correlates of hepatitis C virus-associated inflammatory arthritis in a population-based cohort. Semin Arthritis Rheum. 2017;47:445-450. doi: 10.1016/j.semarthrit.2017.04.004
3. Arora S, Kalishman S, Thornton K, et al. Expanding access to hepatitis C virus treatment--Extension for Community Healthcare Outcomes (ECHO) project: disruptive innovation in specialty care. Hepatology. 2010;52:1124-1133. doi: 10.1002/hep.23802
4. Blecker S, Paul MM, Jones S, et al. A Project ECHO and community health worker intervention for patients with diabetes. Am J Med. 2021;S0002-9343(21)00811-1. doi: 10.1016/j.amjmed.2021.12.002
5. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Accessed June 16, 2023. www.hcvguidelines.org
6. HEP/HIV Drug Interactions Checker University of Liverpool. Interaction Report. Published 2022. Accessed June 26, 2023. www.hep-druginteractions.org/downloads/ajd45jg-4er5-67oy-ur43- 009ert.pdf?interaction_ids%5B%5D=88015&interaction_ids%5B%5D=91366
7. Hong J, Wright RC, Partovi N, et al. Review of clinically relevant drug interactions with next generation hepatitis C direct-acting antiviral agents. J Clin Transl Hepatol. 2020;8:322-335. doi: 10.14218/JCTH.2020.00034
► Large joint arthralgias
► History of type 1 diabetes, seizures, migraines
49-year-old woman • headache and neck pain radiating to ears and eyes • severe hypertension • Dx?
THE CASE
A 49-year-old woman was hospitalized with a headache and neck pain that radiated to her ears and eyes in the context of severe hypertension (270/150 mm Hg). Her medical history was significant for heterozygous factor V Leiden mutation, longstanding untreated hypertension, and multiple severe episodes of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome during pregnancy.
After receiving antihypertensive treatment at a community hospital, her blood pressure gradually improved to 160/100 mm Hg with the addition of a third medication. However, on Day 3 of her stay, her systolic blood pressure rose to more than 200 mm Hg and was accompanied by somnolence, emesis, and paleness. She was transferred to a tertiary care center.
THE DIAGNOSIS
On admission, the patient had left-side hemiparesis and facial droop with dysarthria, resulting in a National Institutes of Health Stroke Scale (NIHSS) score of 7 (out of 42) and a Glasgow Coma Scale (GCS) score of 13 (out of 15). Noncontrast computed tomography (CT) and CT angiography of the head and neck were ordered and showed occlusion of both intracranial vertebral arteries. There were also signs of multifocal infarction in her occipital lobes, thus systemic recombinant human-tissue plasminogen activator (tPA) could not be administered.
The patient was next taken to the angiography suite, where a digital subtraction angiography confirmed the presence of bilateral vertebral artery occlusions (FIGURE 1A). A thrombectomy was performed to open the left occluded segment, resulting in recanalization; however, a high-grade stenosis remained in the intracranial left vertebral artery (FIGURE 1B). The right vertebral artery had a severe extracranial origin stenosis, and balloon angioplasty was performed in order to reach the intracranial circulation; however, the occlusion of the intracranial right vertebral artery segment could not be catheterized. Subsequent magnetic resonance imaging (MRI) with a time-of-flight magnetic resonance angiography showed that the intracranial left vertebral artery with high-grade stenosis had closed down again; thus, there was occlusion of both intracranial vertebral arteries and absent flow signal in the basilar artery (FIGURE 2). There were scattered small acute strokes within the cerebellum, brainstem, and occipital lobes.
Unfortunately, within 48 hours, the patient’s NIHSS score increased from 7 to 29. She developed tetraplegia, was significantly less responsive (GCS score, 3/15), and required intubation and mechanical ventilation. Reopening the stenosis and keeping it open with a stent would be an aggressive procedure with poor odds for success and would require antithrombotic medications with the associated risk for intracranial hemorrhage in the setting of demarcated strokes. Thus, no further intervention was pursued.
Further standard stroke work-up (echocardiography, extracranial ultrasound of the cerebral circulation, and vasculitis screening) was unremarkable. In the intensive care unit, intravenous therapeutic heparin was initiated because of the potential prothrombotic effect of the factor V Leiden mutation but was subsequently switched to dual anti-aggregation therapy (aspirin 100 mg/d and clopidogrel 75 mg/d) as secondary stroke prevention given the final diagnosis of severe atherosclerosis. Nevertheless, the patient remained tetraplegic with a partial locked-in syndrome when she was discharged, after 2 weeks in the tertiary care center, to a rehabilitation center.
DISCUSSION
Posterior circulation strokes account for 20% to 25% of all ischemic strokes1,2 and are associated with infarction within the vertebrobasilar arterial system. Common etiologies of these infarctions include atherosclerosis (as seen in our patient), embolism, small-artery penetrating disease, and arterial dissection.2 Although the estimated overall mortality of these strokes is low (3.6% to 11%),2 basilar occlusion syndrome, in particular, is a life-threatening condition with a high mortality rate of 80% to 90%.3
Continue to: Diagnosis can be particularly challenging...
Diagnosis can be particularly challenging due to the anatomic variations of posterior arterial circulation, as well as the fluctuating nonfocal or multifocal symptoms.2 Specific symptoms include vertigo, ataxia, unilateral motor weakness, dysarthria, and oculomotor dysfunction. However, nonspecific symptoms such as headache, nausea, dizziness, hoarseness, falls, and Horner syndrome may be the only presenting signs of a posterior circulation stroke—as was the case with our patient.2 Her radiating neck pain could have been interpreted as a pointer to vertebral artery dissection within the context of severe hypertension.4 Unfortunately, the diagnosis was delayed and head imaging was obtained only after her mental status deteriorated.
Immediate neuroimaging is necessary to guide treatment in patients with suspected acute posterior circulation stroke,1,5,6 although it is not always definitive. While CT is pivotal in stroke work-up and may reliably exclude intracranial hemorrhage, its ability to detect acute posterior circulation ischemic strokes is limited given its poor visualization of the posterior fossa (as low as 16% sensitivity).5 Fortunately, CT angiography has a high sensitivity (nearing 100%) for large-vessel occlusion and high predictive values for dissection (65%-100% positive predictive value and 70%-98% negative predictive value).5,7 Diffusion-weighted MRI (when available in the emergency setting) has the highest sensitivity for detecting acute infarcts, although posterior circulation infarcts still can be missed (19% false-negative rate).5,8 Thus, correlative vessel imaging with magnetic resonance or CT angiography is very important, along with a high index of suspicion. In some instances, repeat MRI may be necessary to detect small strokes.
A patient-specific approach to management is key for individuals with suspected posterior circulation stroke.5 Because specific data for the appropriate management of posterior circulation ischemic stroke are lacking, current American Heart Association/American Stroke Association (AHA/ASA) guidelines apply to anterior and posterior circulation strokes.6 For eligible patients without multifocal disease, intravenous tPA is the first-line therapy and should be initiated according to guidelines within 4.5 hours of stroke onset9; it is important to note that these guidelines are based on studies that focused more on anterior circulation strokes than posterior circulation strokes.6,9-13 This can be done in combination with endovascular therapy, which consists of mechanical thrombectomy, intra-arterial thrombolysis, or a combination of revascularization techniques.3,5,6
Mechanical thrombectomy specifically has high proven recanalization rates for all target vessels.3-6 The latest AHA/ASA guidelines recommend mechanical thrombectomy be performed within 6 hours of stroke onset.6 However, there is emerging evidence that suggests this timeframe should be extended—even beyond 24 hours—given the poor prognosis of posterior circulation strokes.5,6,14 More data on the management of posterior circulation strokes are urgently needed to better understand which therapeutic approach is most efficient.
In patients such as ours, who have evidence of multifocal disease, treatment may be limited to endovascular therapy. Intracranial stenting of symptomatic lesions in particular has been controversial since the publication of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial, which found that aggressive medical management was superior to stenting in patients who recently had a transient ischemic attack or stroke attributed to stenosis.15 Although additional studies have been performed, there are no definitive data on the topic—and certainly no data in the emergency setting.16 Further challenges are raised in patients with bilateral disease, as was the case with this patient.
When our patient was admitted to the rehabilitation clinic, she had a GCS score of 10 to 11/15. After 9 months of rehabilitation, she was discharged home with a GCS score of 15/15 and persistent left-side hemiparesis.
THE TAKEAWAY
Posterior circulation stroke is a life-threatening disease that may manifest with a variety of symptoms and be difficult to identify on emergent imaging. Thus, a high degree of clinical suspicion and additional follow-up are paramount to ensure prompt diagnosis and a patient-tailored treatment strategy.
CORRESPONDENCE
Kristine A. Blackham, MD, Associate Professor, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; kristine.blackham@gmail.com Orcid no: 0000-0002-1620-1144 (Dr. Blackham); 0000-0002- 5225-5414 (Dr. Saleh)
1. Cloud GC, Markus HS. Diagnosis and management of vertebral artery stenosis. QJM. 2003;96:27-54. doi: 10.1093/qjmed/hcg003
2. Sparaco M, Ciolli L, Zini A. Posterior circulation ischaemic stroke–a review part I: anatomy, aetiology and clinical presentations. Neurol Sci. 2019;40:1995-2006. doi: 10.1007/s10072-019-03977-2
3. Lin DDM, Gailloud P, Beauchamp NJ, et al. Combined stent placement and thrombolysis in acute vertebrobasilar ischemic stroke. AJNR Am J Neuroradiol. 2003;24:1827-1833.
4. Pezzini A, Caso V, Zanferrari C, et al. Arterial hypertension as risk factor for spontaneous cervical artery dissection. A case-control study. J Neurol Neurosurg Psychiatry. 2006;77:95-97. doi:10.1136/jnnp.2005.063107
5. Merwick Á, Werring D. Posterior circulation ischaemic stroke. BMJ. 2014;348:g3175. doi: 10.1136/bmj.g3175
6. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110. doi: 10.1161/STR.0000000000000158
7. Provenzale JM, Sarikaya B. Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature. AJR Am J Roentgenol. 2009;193:1167-1174. doi: 10.2214/AJR.08.1688
8. Husnoo Q. A case of missed diagnosis of posterior circulation stroke. Clin Med (Lond). 2019;19(suppl 2):63. doi: 10.7861/clinmedicine.19-2-s63
9. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317-1329. doi: 10.1056/NEJMoa0804656
10. Schneider AM, Neuhaus AA, Hadley G, et al. Posterior circulation ischaemic stroke diagnosis and management. Clin Med (Lond). 2023;23:219-227. doi: 10.7861/clinmed.2022-0499
11. Dorňák T, Král M, Šaňák D, et al. Intravenous thrombolysis in posterior circulation stroke. Front Neurol. 2019;10:417. doi: 10.3389/fneur.2019.00417
12. van der Hoeven EJ, Schonewille WJ, Vos JA, et al. The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial. Trials. 2013;14:200. doi: 10.1186/1745-6215-14-200
13. Nouh A, Remke J, Ruland S. Ischemic posterior circulation stroke: a review of anatomy, clinical presentations, diagnosis, and current management. Front Neurol. 2014;5:30. doi: 10.3389/fneur.2014.00030
14. Purrucker JC, Ringleb PA, Seker F, et al. Leaving the day behind: endovascular therapy beyond 24 h in acute stroke of the anterior and posterior circulation. Ther Adv Neurol Disord. 2022;15:17562864221101083. doi: 10.1177/17562864221101083
15. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993-1003. doi: 10.1056/NEJMoa1105335
16. Markus HS, Michel P. Treatment of posterior circulation stroke: acute management and secondary prevention. Int J Stroke. 2022;17:723-732. doi: 10.1177/17474930221107500
THE CASE
A 49-year-old woman was hospitalized with a headache and neck pain that radiated to her ears and eyes in the context of severe hypertension (270/150 mm Hg). Her medical history was significant for heterozygous factor V Leiden mutation, longstanding untreated hypertension, and multiple severe episodes of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome during pregnancy.
After receiving antihypertensive treatment at a community hospital, her blood pressure gradually improved to 160/100 mm Hg with the addition of a third medication. However, on Day 3 of her stay, her systolic blood pressure rose to more than 200 mm Hg and was accompanied by somnolence, emesis, and paleness. She was transferred to a tertiary care center.
THE DIAGNOSIS
On admission, the patient had left-side hemiparesis and facial droop with dysarthria, resulting in a National Institutes of Health Stroke Scale (NIHSS) score of 7 (out of 42) and a Glasgow Coma Scale (GCS) score of 13 (out of 15). Noncontrast computed tomography (CT) and CT angiography of the head and neck were ordered and showed occlusion of both intracranial vertebral arteries. There were also signs of multifocal infarction in her occipital lobes, thus systemic recombinant human-tissue plasminogen activator (tPA) could not be administered.
The patient was next taken to the angiography suite, where a digital subtraction angiography confirmed the presence of bilateral vertebral artery occlusions (FIGURE 1A). A thrombectomy was performed to open the left occluded segment, resulting in recanalization; however, a high-grade stenosis remained in the intracranial left vertebral artery (FIGURE 1B). The right vertebral artery had a severe extracranial origin stenosis, and balloon angioplasty was performed in order to reach the intracranial circulation; however, the occlusion of the intracranial right vertebral artery segment could not be catheterized. Subsequent magnetic resonance imaging (MRI) with a time-of-flight magnetic resonance angiography showed that the intracranial left vertebral artery with high-grade stenosis had closed down again; thus, there was occlusion of both intracranial vertebral arteries and absent flow signal in the basilar artery (FIGURE 2). There were scattered small acute strokes within the cerebellum, brainstem, and occipital lobes.
Unfortunately, within 48 hours, the patient’s NIHSS score increased from 7 to 29. She developed tetraplegia, was significantly less responsive (GCS score, 3/15), and required intubation and mechanical ventilation. Reopening the stenosis and keeping it open with a stent would be an aggressive procedure with poor odds for success and would require antithrombotic medications with the associated risk for intracranial hemorrhage in the setting of demarcated strokes. Thus, no further intervention was pursued.
Further standard stroke work-up (echocardiography, extracranial ultrasound of the cerebral circulation, and vasculitis screening) was unremarkable. In the intensive care unit, intravenous therapeutic heparin was initiated because of the potential prothrombotic effect of the factor V Leiden mutation but was subsequently switched to dual anti-aggregation therapy (aspirin 100 mg/d and clopidogrel 75 mg/d) as secondary stroke prevention given the final diagnosis of severe atherosclerosis. Nevertheless, the patient remained tetraplegic with a partial locked-in syndrome when she was discharged, after 2 weeks in the tertiary care center, to a rehabilitation center.
DISCUSSION
Posterior circulation strokes account for 20% to 25% of all ischemic strokes1,2 and are associated with infarction within the vertebrobasilar arterial system. Common etiologies of these infarctions include atherosclerosis (as seen in our patient), embolism, small-artery penetrating disease, and arterial dissection.2 Although the estimated overall mortality of these strokes is low (3.6% to 11%),2 basilar occlusion syndrome, in particular, is a life-threatening condition with a high mortality rate of 80% to 90%.3
Continue to: Diagnosis can be particularly challenging...
Diagnosis can be particularly challenging due to the anatomic variations of posterior arterial circulation, as well as the fluctuating nonfocal or multifocal symptoms.2 Specific symptoms include vertigo, ataxia, unilateral motor weakness, dysarthria, and oculomotor dysfunction. However, nonspecific symptoms such as headache, nausea, dizziness, hoarseness, falls, and Horner syndrome may be the only presenting signs of a posterior circulation stroke—as was the case with our patient.2 Her radiating neck pain could have been interpreted as a pointer to vertebral artery dissection within the context of severe hypertension.4 Unfortunately, the diagnosis was delayed and head imaging was obtained only after her mental status deteriorated.
Immediate neuroimaging is necessary to guide treatment in patients with suspected acute posterior circulation stroke,1,5,6 although it is not always definitive. While CT is pivotal in stroke work-up and may reliably exclude intracranial hemorrhage, its ability to detect acute posterior circulation ischemic strokes is limited given its poor visualization of the posterior fossa (as low as 16% sensitivity).5 Fortunately, CT angiography has a high sensitivity (nearing 100%) for large-vessel occlusion and high predictive values for dissection (65%-100% positive predictive value and 70%-98% negative predictive value).5,7 Diffusion-weighted MRI (when available in the emergency setting) has the highest sensitivity for detecting acute infarcts, although posterior circulation infarcts still can be missed (19% false-negative rate).5,8 Thus, correlative vessel imaging with magnetic resonance or CT angiography is very important, along with a high index of suspicion. In some instances, repeat MRI may be necessary to detect small strokes.
A patient-specific approach to management is key for individuals with suspected posterior circulation stroke.5 Because specific data for the appropriate management of posterior circulation ischemic stroke are lacking, current American Heart Association/American Stroke Association (AHA/ASA) guidelines apply to anterior and posterior circulation strokes.6 For eligible patients without multifocal disease, intravenous tPA is the first-line therapy and should be initiated according to guidelines within 4.5 hours of stroke onset9; it is important to note that these guidelines are based on studies that focused more on anterior circulation strokes than posterior circulation strokes.6,9-13 This can be done in combination with endovascular therapy, which consists of mechanical thrombectomy, intra-arterial thrombolysis, or a combination of revascularization techniques.3,5,6
Mechanical thrombectomy specifically has high proven recanalization rates for all target vessels.3-6 The latest AHA/ASA guidelines recommend mechanical thrombectomy be performed within 6 hours of stroke onset.6 However, there is emerging evidence that suggests this timeframe should be extended—even beyond 24 hours—given the poor prognosis of posterior circulation strokes.5,6,14 More data on the management of posterior circulation strokes are urgently needed to better understand which therapeutic approach is most efficient.
In patients such as ours, who have evidence of multifocal disease, treatment may be limited to endovascular therapy. Intracranial stenting of symptomatic lesions in particular has been controversial since the publication of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial, which found that aggressive medical management was superior to stenting in patients who recently had a transient ischemic attack or stroke attributed to stenosis.15 Although additional studies have been performed, there are no definitive data on the topic—and certainly no data in the emergency setting.16 Further challenges are raised in patients with bilateral disease, as was the case with this patient.
When our patient was admitted to the rehabilitation clinic, she had a GCS score of 10 to 11/15. After 9 months of rehabilitation, she was discharged home with a GCS score of 15/15 and persistent left-side hemiparesis.
THE TAKEAWAY
Posterior circulation stroke is a life-threatening disease that may manifest with a variety of symptoms and be difficult to identify on emergent imaging. Thus, a high degree of clinical suspicion and additional follow-up are paramount to ensure prompt diagnosis and a patient-tailored treatment strategy.
CORRESPONDENCE
Kristine A. Blackham, MD, Associate Professor, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; kristine.blackham@gmail.com Orcid no: 0000-0002-1620-1144 (Dr. Blackham); 0000-0002- 5225-5414 (Dr. Saleh)
THE CASE
A 49-year-old woman was hospitalized with a headache and neck pain that radiated to her ears and eyes in the context of severe hypertension (270/150 mm Hg). Her medical history was significant for heterozygous factor V Leiden mutation, longstanding untreated hypertension, and multiple severe episodes of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome during pregnancy.
After receiving antihypertensive treatment at a community hospital, her blood pressure gradually improved to 160/100 mm Hg with the addition of a third medication. However, on Day 3 of her stay, her systolic blood pressure rose to more than 200 mm Hg and was accompanied by somnolence, emesis, and paleness. She was transferred to a tertiary care center.
THE DIAGNOSIS
On admission, the patient had left-side hemiparesis and facial droop with dysarthria, resulting in a National Institutes of Health Stroke Scale (NIHSS) score of 7 (out of 42) and a Glasgow Coma Scale (GCS) score of 13 (out of 15). Noncontrast computed tomography (CT) and CT angiography of the head and neck were ordered and showed occlusion of both intracranial vertebral arteries. There were also signs of multifocal infarction in her occipital lobes, thus systemic recombinant human-tissue plasminogen activator (tPA) could not be administered.
The patient was next taken to the angiography suite, where a digital subtraction angiography confirmed the presence of bilateral vertebral artery occlusions (FIGURE 1A). A thrombectomy was performed to open the left occluded segment, resulting in recanalization; however, a high-grade stenosis remained in the intracranial left vertebral artery (FIGURE 1B). The right vertebral artery had a severe extracranial origin stenosis, and balloon angioplasty was performed in order to reach the intracranial circulation; however, the occlusion of the intracranial right vertebral artery segment could not be catheterized. Subsequent magnetic resonance imaging (MRI) with a time-of-flight magnetic resonance angiography showed that the intracranial left vertebral artery with high-grade stenosis had closed down again; thus, there was occlusion of both intracranial vertebral arteries and absent flow signal in the basilar artery (FIGURE 2). There were scattered small acute strokes within the cerebellum, brainstem, and occipital lobes.
Unfortunately, within 48 hours, the patient’s NIHSS score increased from 7 to 29. She developed tetraplegia, was significantly less responsive (GCS score, 3/15), and required intubation and mechanical ventilation. Reopening the stenosis and keeping it open with a stent would be an aggressive procedure with poor odds for success and would require antithrombotic medications with the associated risk for intracranial hemorrhage in the setting of demarcated strokes. Thus, no further intervention was pursued.
Further standard stroke work-up (echocardiography, extracranial ultrasound of the cerebral circulation, and vasculitis screening) was unremarkable. In the intensive care unit, intravenous therapeutic heparin was initiated because of the potential prothrombotic effect of the factor V Leiden mutation but was subsequently switched to dual anti-aggregation therapy (aspirin 100 mg/d and clopidogrel 75 mg/d) as secondary stroke prevention given the final diagnosis of severe atherosclerosis. Nevertheless, the patient remained tetraplegic with a partial locked-in syndrome when she was discharged, after 2 weeks in the tertiary care center, to a rehabilitation center.
DISCUSSION
Posterior circulation strokes account for 20% to 25% of all ischemic strokes1,2 and are associated with infarction within the vertebrobasilar arterial system. Common etiologies of these infarctions include atherosclerosis (as seen in our patient), embolism, small-artery penetrating disease, and arterial dissection.2 Although the estimated overall mortality of these strokes is low (3.6% to 11%),2 basilar occlusion syndrome, in particular, is a life-threatening condition with a high mortality rate of 80% to 90%.3
Continue to: Diagnosis can be particularly challenging...
Diagnosis can be particularly challenging due to the anatomic variations of posterior arterial circulation, as well as the fluctuating nonfocal or multifocal symptoms.2 Specific symptoms include vertigo, ataxia, unilateral motor weakness, dysarthria, and oculomotor dysfunction. However, nonspecific symptoms such as headache, nausea, dizziness, hoarseness, falls, and Horner syndrome may be the only presenting signs of a posterior circulation stroke—as was the case with our patient.2 Her radiating neck pain could have been interpreted as a pointer to vertebral artery dissection within the context of severe hypertension.4 Unfortunately, the diagnosis was delayed and head imaging was obtained only after her mental status deteriorated.
Immediate neuroimaging is necessary to guide treatment in patients with suspected acute posterior circulation stroke,1,5,6 although it is not always definitive. While CT is pivotal in stroke work-up and may reliably exclude intracranial hemorrhage, its ability to detect acute posterior circulation ischemic strokes is limited given its poor visualization of the posterior fossa (as low as 16% sensitivity).5 Fortunately, CT angiography has a high sensitivity (nearing 100%) for large-vessel occlusion and high predictive values for dissection (65%-100% positive predictive value and 70%-98% negative predictive value).5,7 Diffusion-weighted MRI (when available in the emergency setting) has the highest sensitivity for detecting acute infarcts, although posterior circulation infarcts still can be missed (19% false-negative rate).5,8 Thus, correlative vessel imaging with magnetic resonance or CT angiography is very important, along with a high index of suspicion. In some instances, repeat MRI may be necessary to detect small strokes.
A patient-specific approach to management is key for individuals with suspected posterior circulation stroke.5 Because specific data for the appropriate management of posterior circulation ischemic stroke are lacking, current American Heart Association/American Stroke Association (AHA/ASA) guidelines apply to anterior and posterior circulation strokes.6 For eligible patients without multifocal disease, intravenous tPA is the first-line therapy and should be initiated according to guidelines within 4.5 hours of stroke onset9; it is important to note that these guidelines are based on studies that focused more on anterior circulation strokes than posterior circulation strokes.6,9-13 This can be done in combination with endovascular therapy, which consists of mechanical thrombectomy, intra-arterial thrombolysis, or a combination of revascularization techniques.3,5,6
Mechanical thrombectomy specifically has high proven recanalization rates for all target vessels.3-6 The latest AHA/ASA guidelines recommend mechanical thrombectomy be performed within 6 hours of stroke onset.6 However, there is emerging evidence that suggests this timeframe should be extended—even beyond 24 hours—given the poor prognosis of posterior circulation strokes.5,6,14 More data on the management of posterior circulation strokes are urgently needed to better understand which therapeutic approach is most efficient.
In patients such as ours, who have evidence of multifocal disease, treatment may be limited to endovascular therapy. Intracranial stenting of symptomatic lesions in particular has been controversial since the publication of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial, which found that aggressive medical management was superior to stenting in patients who recently had a transient ischemic attack or stroke attributed to stenosis.15 Although additional studies have been performed, there are no definitive data on the topic—and certainly no data in the emergency setting.16 Further challenges are raised in patients with bilateral disease, as was the case with this patient.
When our patient was admitted to the rehabilitation clinic, she had a GCS score of 10 to 11/15. After 9 months of rehabilitation, she was discharged home with a GCS score of 15/15 and persistent left-side hemiparesis.
THE TAKEAWAY
Posterior circulation stroke is a life-threatening disease that may manifest with a variety of symptoms and be difficult to identify on emergent imaging. Thus, a high degree of clinical suspicion and additional follow-up are paramount to ensure prompt diagnosis and a patient-tailored treatment strategy.
CORRESPONDENCE
Kristine A. Blackham, MD, Associate Professor, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; kristine.blackham@gmail.com Orcid no: 0000-0002-1620-1144 (Dr. Blackham); 0000-0002- 5225-5414 (Dr. Saleh)
1. Cloud GC, Markus HS. Diagnosis and management of vertebral artery stenosis. QJM. 2003;96:27-54. doi: 10.1093/qjmed/hcg003
2. Sparaco M, Ciolli L, Zini A. Posterior circulation ischaemic stroke–a review part I: anatomy, aetiology and clinical presentations. Neurol Sci. 2019;40:1995-2006. doi: 10.1007/s10072-019-03977-2
3. Lin DDM, Gailloud P, Beauchamp NJ, et al. Combined stent placement and thrombolysis in acute vertebrobasilar ischemic stroke. AJNR Am J Neuroradiol. 2003;24:1827-1833.
4. Pezzini A, Caso V, Zanferrari C, et al. Arterial hypertension as risk factor for spontaneous cervical artery dissection. A case-control study. J Neurol Neurosurg Psychiatry. 2006;77:95-97. doi:10.1136/jnnp.2005.063107
5. Merwick Á, Werring D. Posterior circulation ischaemic stroke. BMJ. 2014;348:g3175. doi: 10.1136/bmj.g3175
6. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110. doi: 10.1161/STR.0000000000000158
7. Provenzale JM, Sarikaya B. Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature. AJR Am J Roentgenol. 2009;193:1167-1174. doi: 10.2214/AJR.08.1688
8. Husnoo Q. A case of missed diagnosis of posterior circulation stroke. Clin Med (Lond). 2019;19(suppl 2):63. doi: 10.7861/clinmedicine.19-2-s63
9. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317-1329. doi: 10.1056/NEJMoa0804656
10. Schneider AM, Neuhaus AA, Hadley G, et al. Posterior circulation ischaemic stroke diagnosis and management. Clin Med (Lond). 2023;23:219-227. doi: 10.7861/clinmed.2022-0499
11. Dorňák T, Král M, Šaňák D, et al. Intravenous thrombolysis in posterior circulation stroke. Front Neurol. 2019;10:417. doi: 10.3389/fneur.2019.00417
12. van der Hoeven EJ, Schonewille WJ, Vos JA, et al. The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial. Trials. 2013;14:200. doi: 10.1186/1745-6215-14-200
13. Nouh A, Remke J, Ruland S. Ischemic posterior circulation stroke: a review of anatomy, clinical presentations, diagnosis, and current management. Front Neurol. 2014;5:30. doi: 10.3389/fneur.2014.00030
14. Purrucker JC, Ringleb PA, Seker F, et al. Leaving the day behind: endovascular therapy beyond 24 h in acute stroke of the anterior and posterior circulation. Ther Adv Neurol Disord. 2022;15:17562864221101083. doi: 10.1177/17562864221101083
15. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993-1003. doi: 10.1056/NEJMoa1105335
16. Markus HS, Michel P. Treatment of posterior circulation stroke: acute management and secondary prevention. Int J Stroke. 2022;17:723-732. doi: 10.1177/17474930221107500
1. Cloud GC, Markus HS. Diagnosis and management of vertebral artery stenosis. QJM. 2003;96:27-54. doi: 10.1093/qjmed/hcg003
2. Sparaco M, Ciolli L, Zini A. Posterior circulation ischaemic stroke–a review part I: anatomy, aetiology and clinical presentations. Neurol Sci. 2019;40:1995-2006. doi: 10.1007/s10072-019-03977-2
3. Lin DDM, Gailloud P, Beauchamp NJ, et al. Combined stent placement and thrombolysis in acute vertebrobasilar ischemic stroke. AJNR Am J Neuroradiol. 2003;24:1827-1833.
4. Pezzini A, Caso V, Zanferrari C, et al. Arterial hypertension as risk factor for spontaneous cervical artery dissection. A case-control study. J Neurol Neurosurg Psychiatry. 2006;77:95-97. doi:10.1136/jnnp.2005.063107
5. Merwick Á, Werring D. Posterior circulation ischaemic stroke. BMJ. 2014;348:g3175. doi: 10.1136/bmj.g3175
6. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110. doi: 10.1161/STR.0000000000000158
7. Provenzale JM, Sarikaya B. Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature. AJR Am J Roentgenol. 2009;193:1167-1174. doi: 10.2214/AJR.08.1688
8. Husnoo Q. A case of missed diagnosis of posterior circulation stroke. Clin Med (Lond). 2019;19(suppl 2):63. doi: 10.7861/clinmedicine.19-2-s63
9. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317-1329. doi: 10.1056/NEJMoa0804656
10. Schneider AM, Neuhaus AA, Hadley G, et al. Posterior circulation ischaemic stroke diagnosis and management. Clin Med (Lond). 2023;23:219-227. doi: 10.7861/clinmed.2022-0499
11. Dorňák T, Král M, Šaňák D, et al. Intravenous thrombolysis in posterior circulation stroke. Front Neurol. 2019;10:417. doi: 10.3389/fneur.2019.00417
12. van der Hoeven EJ, Schonewille WJ, Vos JA, et al. The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial. Trials. 2013;14:200. doi: 10.1186/1745-6215-14-200
13. Nouh A, Remke J, Ruland S. Ischemic posterior circulation stroke: a review of anatomy, clinical presentations, diagnosis, and current management. Front Neurol. 2014;5:30. doi: 10.3389/fneur.2014.00030
14. Purrucker JC, Ringleb PA, Seker F, et al. Leaving the day behind: endovascular therapy beyond 24 h in acute stroke of the anterior and posterior circulation. Ther Adv Neurol Disord. 2022;15:17562864221101083. doi: 10.1177/17562864221101083
15. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993-1003. doi: 10.1056/NEJMoa1105335
16. Markus HS, Michel P. Treatment of posterior circulation stroke: acute management and secondary prevention. Int J Stroke. 2022;17:723-732. doi: 10.1177/17474930221107500
► Headache and neck pain radiating to ears and eyes
► Severe hypertension
