Clinical Topics & News

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

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

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

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

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

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

After more than 600,000 deaths in the United States from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several safe and effective vaccines against the virus have become available. Vaccines are the most effective preventive measure against COVID-19 and the most promising way to achieve herd immunity to end the current pandemic. However, obstacles to reaching this goal include vaccine skepticism, structural barriers, or simple inertia to get vaccinated. These challenges provide opportunities for psychiatrists to use their medical knowledge and expertise, applying behavior management techniques such as motivational interviewing and nudging to encourage their patients to get vaccinated. In particular, marginalized patients with serious mental illness (SMI), who are subject to disproportionately high rates of COVID-19 infection and more severe outcomes,¹ have much to gain if psychiatrists become involved in the COVID-19 vaccination campaign.

In this article, we define vaccine hesitancy and highlight what makes psychiatrists ideal vaccine ambassadors, given their unique skill set and longitudinal, trust-based connection with their patients. We expand on the particular vulnerabilities of patients with SMI, including structural barriers to vaccination that lead to health disparities and inequity. Finally, building on “The ABCs of successful vaccinations” framework published in Current Psychiatry March 2021,² we outline how psychiatrists can address vaccine misconceptions, employ effective communication strategies to build vaccine confidence, and help patients overcome structural barriers and get the COVID-19 vaccination. While we are currently focused on ending the COVID-19 pandemic, our broader mission as psychiatrists should be to become ambassadors for other vaccinations as well, such as the annual influenza vaccine.

What is vaccine hesitancy?

The World Health Organization (WHO) defines vaccine hesitancy as a “delay in acceptance or refusal of vaccines despite availability of vaccine services.”^3,4 Vaccine hesitancy occurs on a continuum ranging from uncertainty about accepting a vaccine to absolute refusal.^4,5 It involves a complex decision-making process driven by contextual, individual, and social influences, and vaccine-specific issues.⁴ In the “3C” model developed by the WHO Strategic Advisory Group of Experts (SAGE) Working Group, vaccine hesitancy is influenced by confidence (trust in vaccines, in the health care system, and in policy makers), complacency (lower perceived risk), and convenience (availability, affordability, accessibility, language and health literacy, appeal of vaccination program).⁴

In 2019, the WHO named vaccine hesitancy as one of the top 10 global health threats.³ Hesitancy to receive COVID-19 vaccines may be particularly high because of their rapid development. In addition, the tumultuous political environment that often featured inconsistent messaging about the virus, its dangers, and its transmission since the early days of the pandemic created widespread public confusion and doubt as scientific understandings evolved. “Anti-vaxxer” movements that completely rejected vaccine efficacy disseminated misinformation online. Followers of these movements may have such extreme overvalued ideas that any effort to persuade them otherwise with scientific evidence will accomplish very little.^6,7 Therefore, focusing on individuals who are “sitting on the fence” about getting vaccinated can be more productive because they represent a much larger group than those who adamantly refuse vaccines, and they may be more amenable to changing beliefs and behaviors.⁸

The US Census Bureau’s Household Pulse Survey asked, “How likely are you to accept the vaccine?”⁹ As of late June 2021, 11.4% of US adults reported they would “definitely not get a vaccine” or “probably not get a vaccine,” and that number increases to 16.9% when including those who are “unsure,” although there is wide geographical variability.¹⁰

A recent study in Denmark showed that willingness to receive the COVID-19 vaccine was slightly lower among patients with mental illness (84.8%) compared with the general population (89.5%).¹¹ Given the small difference, vaccine hesitancy was not considered to be a major barrier for vaccination among patients with mental illness in Denmark. This is similar to the findings of a pre-pandemic study at a community mental health clinic in the United States involving other vaccinations, which suggested that 84% of patients with SMI perceived vaccinations as safe, effective, and important.¹² In this clinic, identified barriers to vaccinations in general among patients with SMI included lack of awareness and knowledge (42.2%), accessibility (16.3%), personal cost (13.3%), fears about immunization (10.4%), and lack of recommendations by primary care providers (PCPs) (1.5%).¹²

It is critical to distinguish attitude-driven vaccine hesitancy from a lack of education and opportunity to receive a vaccine. Particularly disadvantaged communities may be mislabeled as “vaccine hesitant” when in fact they may not have the ability to be as proactive as other population groups (eg, difficulty scheduling appointments over the Internet).

Continue to: What makes psychiatrists ideal vaccine ambassadors?

What makes psychiatrists ideal vaccine ambassadors?

There are several reasons psychiatrists can be well-positioned to contribute to the success of vaccination campaigns (Table 1). These include their frequent contact with patients and their care teams, the high trust those patients have in them, and their medical expertise and skills in applied behavioral and social science techniques, including motivational interviewing and nudging. Vaccination efforts and outreach are more effective when led by the clinician with whom the patient has the most contact because resolving vaccine hesitancy is not a one-time discussion but requires ongoing communication, persistence, and consistency.¹³ Patients may contact their psychiatrists more frequently than their other clinicians, including PCPs. For this reason, psychiatrists can serve as the gateway to health care, particularly for patients with SMI.¹⁴ In addition, interruptions in nonemergency services caused by the COVID-19 pandemic may affect vaccine delivery because patients may have been unable to see their PCPs regularly during the pandemic.¹⁵

Psychiatrists’ medical expertise and their ability to develop rapport with their patients promote trust-building. Receiving credible information from a trusted source such as a patient’s psychiatrist can be impactful. A recent poll suggested that individual health care clinicians have been consistently identified as the most trusted sources for vaccine information, including for the COVID-19 vaccines.¹⁶ There is also higher trust when there is greater continuity of care both in terms of length of time the patient has known the clinician and the number of consultations,¹⁷ an inherent part of psychiatric practice. In addition, research has shown that patients trust their psychiatrists as much as they trust their general practitioners.¹⁸

Psychiatrists are experts in behavior change, promoting healthy behaviors through motivational interviewing and nudging. They also have experience with managing patients who hold overvalued ideas as well as dealing with uncertainty, given their scientific and medical training.

Motivational interviewing is a patient-centered, collaborative approach widely used by psychiatrists to treat unhealthy behaviors such as substance use. Clinicians elicit and strengthen the patient’s desire and motivation for change while respecting their autonomy. Instead of presenting persuasive facts, the clinician creates a welcoming, nonthreatening, safe environment by engaging patients in open dialogue, reflecting back the patients’ concerns with empathy, helping them realize contradictions in behavior, and supporting self-sufficiency.¹⁹ In a nonpsychiatric setting, studies have shown the effectiveness of motivational interviewing in increasing uptake of human papillomavirus vaccines and of pediatric vaccines.²⁰

Nudging, which comes from behavioral economics and psychology, underscores the importance of structuring a choice architecture in changing the way people make their everyday decisions.²¹ Nudging still gives people a choice and respects autonomy, but it leads patients to more efficient and productive decision-making. Many nudges are based around giving good “default options” because people often do not make efforts to deviate from default options. In addition, social nudges are powerful, giving people a social reference point and normalizing certain behaviors.²¹ Psychiatrists have become skilled in nudging from working with patients with varying levels of insight and cognitive capabilities. That is, they give simple choices, prompts, and frequent feedback to reinforce “good” decisions and to discourage “bad” decisions.

Continue to: Managing overvalued ideas

Managing overvalued ideas. Psychiatrists are also well-versed in having discussions with patients who hold irrational beliefs (psychosis) or overvalued ideas. For example, psychiatrists frequently manage anorexia nervosa and hypochondria, which are rooted in overvalued ideas.⁷ While psychiatrists may not be able to directly confront the overvalued ideas, they can work around such ideas while waiting for more flexible moments. Similarly, managing patients with intense emotional commitment⁷ to commonly held anti-vaccination ideas may not be much different. Psychiatrists can work around resistance until patients may be less strongly attached to those overvalued ideas in instances when other techniques, such as motivational interviewing and nudging, may be more effective.

Managing uncertainty. Psychiatrists are experts in managing “not knowing” and uncertainty. Due to their medical scientific training, they are familiar with the process of science, and how understanding changes through trial and error. In contrast, most patients usually only see the end product (ie, a drug comes to market). Discussions with patients that acknowledge uncertainty and emphasize that changes in what is known are expected and appropriate as scientific knowledge evolves could help preempt skepticism when messages are updated.
 

Why do patients with SMI need more help?

SMI as a high-risk group. Patients with SMI are part of a “tragic” epidemiologic triad of agent-host-environment¹⁵ that places them at remarkably elevated risk for COVID-19 infection and more serious complications and death when infected.¹ After age, a diagnosis of a schizophrenia spectrum disorder is the second largest predictor of mortality from COVID-19, with a 2.7-fold increase in mortality.²² This is how the elements of the triad come together: SARS-Cov-2 is a highly infectious agent affecting individuals who are vulnerable hosts because of their high frequency of medical comorbidities, including cardio­vascular disease, type 2 diabetes, and respiratory tract diseases, which are all risk factors for worse outcomes due to COVID-19.²³ In addition, SMI is associated with socioeconomic risk factors for SARS-Cov-2 infection, including poverty, homelessness, and crowded settings such as jails, group homes, hospitals, and shelters, which constitute ideal environments for high transmission of the virus.

Structural barriers to vaccination. Studies have suggested lower rates of vaccination among people with SMI for various other infectious diseases compared with the general population.¹² For example, in 1 outpatient mental health setting, influenza vaccination rates were 24% to 28%, which was lower than the national vaccination rate of 40.9% for the same influenza season (2010 to 2011).²⁴ More recently, a study in Israel examining the COVID-19 vaccination rate among >25,000 patients with schizophrenia suggested under-vaccination of this cohort. The results showed that the odds of getting the COVID-19 vaccination were significantly lower in the schizophrenia group compared with the general population (odds ratio = 0.80, 95% CI: 0.77 to 0.83).²⁵

Patients with SMI encounter considerable system-level barriers to vaccinations in general, such as reduced access to health care due to cost and a lack of transportation,¹² the digital divide given their reduced access to the internet and computers for information and scheduling,²⁶ and lack of vaccination recommendations from their PCPs.¹² Studies have also shown that patients with SMI often receive suboptimal medical care because of stigmatization and discrimination.²⁷ They also have lower rates of preventive care utilization, seeking medical services only in times of crisis and seeking mental health services more often than physical health care.^28-30

Continue to: Patients with SMI face...

Patients with SMI face additional individual challenges that impede vaccine uptake, such as lack of knowledge and awareness about the virus and vaccinations, general cognitive impairment, low digital literacy skills,³¹ low language literacy and educational attainment, baseline delusions, and negative symptoms such as apathy, avolition, and anhedonia.¹ Thus, even if they overcome the external barriers and obtain vaccine-related information, these patients may experience difficulty in understanding the content and applying this information to their personal circumstances as a result of low health literacy.

How psychiatrists can help

The concept of using mental health care sites and trained clinicians to increase medical disease prevention is not new. The rigorously tested intervention model STIRR (Screen, Test, Immunize, Reduce risk, and Refer) uses co-located nurse practitioners in community mental health centers to provide risk assessment, counseling, and blood testing for hepatitis and HIV, as well as on-site vaccinations for hepatitis to patients dually diagnosed with SMI and substance use disorders.³² Similarly, when a vaccination program was integrated into an outpatient mental health clinic offering various on-site vaccinations, vaccination rates increased by up to 25% over baseline.¹² Such public health approaches of integrating medical care at the site of mental health care, where patients with SMI are most reliably engaged, can be highly cost-effective³³ in terms of reducing disease burden among patients with SMI.

While the psychiatrist may not have the time and resources to directly follow through on all aspects of vaccinations, they can assume leadership and work with the larger team—including therapists and counselors, nurse practitioners, social workers, case managers, care coordinators, or PCPs with whom they regularly collaborate in caring for patients with SMI—to communicate what they have learned about patient hesitancies, share suggestions for future conversations to address these hesitancies, and relay what structural barriers the patient may need assistance to address.

Prioritization of patients with SMI for vaccine eligibility does not directly lead to vaccine uptake. Patients with SMI need extra support from their primary point of health care contact, namely their psychiatrists. Psychiatrists may bring a set of specialized skills uniquely suited to this moment to address vaccine hesitancy and overall lack of vaccine resources and awareness. Freudenreich et al² recently proposed “The ABCs of Successful Vaccinations” framework that psychiatrists can use in their interactions with patients to encourage vaccination by focusing on:

• attitudes towards vaccination
• barriers to vaccination
• completed vaccination series.

Understand attitudes toward vaccination. Decision-making may be an emotional and psychological experience that is informed by thoughts and feelings,³⁴ and psychiatrists are uniquely positioned to tailor messages to individual patients by using motivational interviewing and applying nudging techniques.⁸ Given the large role of the pandemic in everyday life, it would be natural to address vaccine-related concerns in the course of routine rapport-building. Table 2^19,34-38 shows example phrases of COVID-19 vaccine messages that are based on communication strategies that have demonstrated success in health behavior domains (including vaccinations).³⁹

Continue to: First, a strong recommendation...

First, a strong recommendation should be made using the presumptive approach.⁴⁰ If vaccine hesitancy is detected, psychiatrists should next attempt to understand patients’ reasoning with open-ended questions to probe vaccine-related concerns. Motivational interviewing can then be used to target the fence sitters (rather than anti-vaxxers).⁶ Psychiatrists can also communicate with therapists about the need for further follow up on patients’ hesitancies.

When assuring patients of vaccine safety and efficacy, it is helpful to explain the vaccine development process, including FDA approval, extensive clinical trials, monitoring, and the distribution process. Providing clear, transparent, accurate information about the risks and benefits of the vaccines is important, as well as monitoring misinformation and developing convincing counter messages that elicit positive emotions toward the vaccines.⁴¹ Examples of messages to counter common vaccine-related concerns and misinformation are shown in Table 3.^42-44

Know the barriers to vaccination. The role of the psychiatrist is to help patients, particularly those with SMIs, overcome logistical barriers and address hesitancy, which are both essential for vaccine uptake. Psychiatrists can help identify actual barriers (eg, transportation, digital access for information and scheduling) and perceived barriers, improve information access, and help patients obtain self-efficacy to take the actions needed to get vaccinated, particularly by collaborating with and communicating these concerns to other social services (Table 4).⁴¹

Monitor for vaccination series completion. Especially for vaccines that require more than a single dose over time, patients need more reminders, nudges, practical support, and encouragement to complete vaccination. A surprising degree of confusion regarding the timing of protection and benefit from the second COVID-19 injection (for the 2-injection vaccines) was uncovered in a recent survey of >1,000 US adults who had received their vaccinations in February 2021.⁴⁵ Attentive monitoring of vaccination series completion by psychiatrists can thus increase the likelihood that a patient will follow through (Table 4).⁴¹ This can be as simple as asking about completion of the series during appointments, but further aided by communicating to the larger care team (social workers, care managers, care coordinators) when identifying that the patient may need further assistance.

The Figure^2,6,7,19,40 summarizes the steps that psychiatrists can take to help patients get vaccinated by assessing attitudes towards vaccination (vaccine hesitancy), helping to remove barriers to vaccination, and ensuring via patient follow-up that a vaccine series is completed.

Continue to: Active involvement is key

Active involvement is key

The active involvement of psychiatrists in COVID-19 vaccination efforts can protect patients from the virus, reduce health disparities among patients with SMI, and promote herd immunity, helping to end the pandemic. Psychiatry practices can serve as ideal platforms to deliver evidence-based COVID-19 vaccine information and encourage vaccine uptake, particularly for marginalized populations.

Vaccination programs in mental health practices can even be conceptualized as a moral mandate in the spirit of addressing distributive injustice. The population management challenges of individual-level barriers and follow-through could be dramatically reduced—if not nearly eliminated—through policy-level changes that allow vaccinations to be administered in places where patients with SMI are already engaged: that is, “shots in arms” in mental health settings. As noted, some studies have shown that mental health settings can play a key role in other preventive care campaigns, such as the annual influenza and hepatitis vaccinations, and thus the incorporation of preventive care need not be limited to just COVID-19 vaccination efforts.

The COVID-19 pandemic is an opportunity to rethink the role of psychiatrists and psychiatric offices and clinics in preventive health care. The health risks and disparities of patients with SMI require the proactive involvement of psychiatrists at both the level of their individual patients and at the federal and state levels to advocate for policy changes that can benefit these populations. Overall, psychiatrists occupy a special role within the medical establishment that enables them to uniquely advocate for patients with SMI and ensure they are not forgotten during the COVID-19 pandemic.

Bottom Line

Psychiatrists could apply behavior management techniques such as motivational interviewing and nudging to address vaccine hesitancy in their patients and move them to accepting the COVID-19 vaccination. This could be particularly valuable for patients with serious mental illness, who face increased risks from COVID-19 and additional barriers to getting vaccinated.

Related Resources

• American Psychiatric Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-Coronavirus
• Baddeley M. Behavioural economics: a very short introduction. Oxford University Press; 2017.
• Centers for Disease Control and Prevention. Vaccines for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/index.html
• Chou W, Burgdorf C, Gaysynsky A, et al. COVID-19 vaccination communication: applying behavioral and social science to address vaccine hesitancy and foster vaccine confidence. National Institutes of Health. Published 2020. https://obssr.od.nih.gov/sites/obssr/files/inline-files/OBSSR_VaccineWhitePaper_FINAL_508.pdf
• Miller WR, Rollnick S. Motivational interviewing: helping people change. Guilford Press; 2012.

After more than 600,000 deaths in the United States from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several safe and effective vaccines against the virus have become available. Vaccines are the most effective preventive measure against COVID-19 and the most promising way to achieve herd immunity to end the current pandemic. However, obstacles to reaching this goal include vaccine skepticism, structural barriers, or simple inertia to get vaccinated. These challenges provide opportunities for psychiatrists to use their medical knowledge and expertise, applying behavior management techniques such as motivational interviewing and nudging to encourage their patients to get vaccinated. In particular, marginalized patients with serious mental illness (SMI), who are subject to disproportionately high rates of COVID-19 infection and more severe outcomes,¹ have much to gain if psychiatrists become involved in the COVID-19 vaccination campaign.

In this article, we define vaccine hesitancy and highlight what makes psychiatrists ideal vaccine ambassadors, given their unique skill set and longitudinal, trust-based connection with their patients. We expand on the particular vulnerabilities of patients with SMI, including structural barriers to vaccination that lead to health disparities and inequity. Finally, building on “The ABCs of successful vaccinations” framework published in Current Psychiatry March 2021,² we outline how psychiatrists can address vaccine misconceptions, employ effective communication strategies to build vaccine confidence, and help patients overcome structural barriers and get the COVID-19 vaccination. While we are currently focused on ending the COVID-19 pandemic, our broader mission as psychiatrists should be to become ambassadors for other vaccinations as well, such as the annual influenza vaccine.

What is vaccine hesitancy?

The World Health Organization (WHO) defines vaccine hesitancy as a “delay in acceptance or refusal of vaccines despite availability of vaccine services.”^3,4 Vaccine hesitancy occurs on a continuum ranging from uncertainty about accepting a vaccine to absolute refusal.^4,5 It involves a complex decision-making process driven by contextual, individual, and social influences, and vaccine-specific issues.⁴ In the “3C” model developed by the WHO Strategic Advisory Group of Experts (SAGE) Working Group, vaccine hesitancy is influenced by confidence (trust in vaccines, in the health care system, and in policy makers), complacency (lower perceived risk), and convenience (availability, affordability, accessibility, language and health literacy, appeal of vaccination program).⁴

In 2019, the WHO named vaccine hesitancy as one of the top 10 global health threats.³ Hesitancy to receive COVID-19 vaccines may be particularly high because of their rapid development. In addition, the tumultuous political environment that often featured inconsistent messaging about the virus, its dangers, and its transmission since the early days of the pandemic created widespread public confusion and doubt as scientific understandings evolved. “Anti-vaxxer” movements that completely rejected vaccine efficacy disseminated misinformation online. Followers of these movements may have such extreme overvalued ideas that any effort to persuade them otherwise with scientific evidence will accomplish very little.^6,7 Therefore, focusing on individuals who are “sitting on the fence” about getting vaccinated can be more productive because they represent a much larger group than those who adamantly refuse vaccines, and they may be more amenable to changing beliefs and behaviors.⁸

The US Census Bureau’s Household Pulse Survey asked, “How likely are you to accept the vaccine?”⁹ As of late June 2021, 11.4% of US adults reported they would “definitely not get a vaccine” or “probably not get a vaccine,” and that number increases to 16.9% when including those who are “unsure,” although there is wide geographical variability.¹⁰

A recent study in Denmark showed that willingness to receive the COVID-19 vaccine was slightly lower among patients with mental illness (84.8%) compared with the general population (89.5%).¹¹ Given the small difference, vaccine hesitancy was not considered to be a major barrier for vaccination among patients with mental illness in Denmark. This is similar to the findings of a pre-pandemic study at a community mental health clinic in the United States involving other vaccinations, which suggested that 84% of patients with SMI perceived vaccinations as safe, effective, and important.¹² In this clinic, identified barriers to vaccinations in general among patients with SMI included lack of awareness and knowledge (42.2%), accessibility (16.3%), personal cost (13.3%), fears about immunization (10.4%), and lack of recommendations by primary care providers (PCPs) (1.5%).¹²

It is critical to distinguish attitude-driven vaccine hesitancy from a lack of education and opportunity to receive a vaccine. Particularly disadvantaged communities may be mislabeled as “vaccine hesitant” when in fact they may not have the ability to be as proactive as other population groups (eg, difficulty scheduling appointments over the Internet).

Continue to: What makes psychiatrists ideal vaccine ambassadors?

What makes psychiatrists ideal vaccine ambassadors?

There are several reasons psychiatrists can be well-positioned to contribute to the success of vaccination campaigns (Table 1). These include their frequent contact with patients and their care teams, the high trust those patients have in them, and their medical expertise and skills in applied behavioral and social science techniques, including motivational interviewing and nudging. Vaccination efforts and outreach are more effective when led by the clinician with whom the patient has the most contact because resolving vaccine hesitancy is not a one-time discussion but requires ongoing communication, persistence, and consistency.¹³ Patients may contact their psychiatrists more frequently than their other clinicians, including PCPs. For this reason, psychiatrists can serve as the gateway to health care, particularly for patients with SMI.¹⁴ In addition, interruptions in nonemergency services caused by the COVID-19 pandemic may affect vaccine delivery because patients may have been unable to see their PCPs regularly during the pandemic.¹⁵

Psychiatrists’ medical expertise and their ability to develop rapport with their patients promote trust-building. Receiving credible information from a trusted source such as a patient’s psychiatrist can be impactful. A recent poll suggested that individual health care clinicians have been consistently identified as the most trusted sources for vaccine information, including for the COVID-19 vaccines.¹⁶ There is also higher trust when there is greater continuity of care both in terms of length of time the patient has known the clinician and the number of consultations,¹⁷ an inherent part of psychiatric practice. In addition, research has shown that patients trust their psychiatrists as much as they trust their general practitioners.¹⁸

Psychiatrists are experts in behavior change, promoting healthy behaviors through motivational interviewing and nudging. They also have experience with managing patients who hold overvalued ideas as well as dealing with uncertainty, given their scientific and medical training.

Motivational interviewing is a patient-centered, collaborative approach widely used by psychiatrists to treat unhealthy behaviors such as substance use. Clinicians elicit and strengthen the patient’s desire and motivation for change while respecting their autonomy. Instead of presenting persuasive facts, the clinician creates a welcoming, nonthreatening, safe environment by engaging patients in open dialogue, reflecting back the patients’ concerns with empathy, helping them realize contradictions in behavior, and supporting self-sufficiency.¹⁹ In a nonpsychiatric setting, studies have shown the effectiveness of motivational interviewing in increasing uptake of human papillomavirus vaccines and of pediatric vaccines.²⁰

Nudging, which comes from behavioral economics and psychology, underscores the importance of structuring a choice architecture in changing the way people make their everyday decisions.²¹ Nudging still gives people a choice and respects autonomy, but it leads patients to more efficient and productive decision-making. Many nudges are based around giving good “default options” because people often do not make efforts to deviate from default options. In addition, social nudges are powerful, giving people a social reference point and normalizing certain behaviors.²¹ Psychiatrists have become skilled in nudging from working with patients with varying levels of insight and cognitive capabilities. That is, they give simple choices, prompts, and frequent feedback to reinforce “good” decisions and to discourage “bad” decisions.

Continue to: Managing overvalued ideas

Managing overvalued ideas. Psychiatrists are also well-versed in having discussions with patients who hold irrational beliefs (psychosis) or overvalued ideas. For example, psychiatrists frequently manage anorexia nervosa and hypochondria, which are rooted in overvalued ideas.⁷ While psychiatrists may not be able to directly confront the overvalued ideas, they can work around such ideas while waiting for more flexible moments. Similarly, managing patients with intense emotional commitment⁷ to commonly held anti-vaccination ideas may not be much different. Psychiatrists can work around resistance until patients may be less strongly attached to those overvalued ideas in instances when other techniques, such as motivational interviewing and nudging, may be more effective.

Managing uncertainty. Psychiatrists are experts in managing “not knowing” and uncertainty. Due to their medical scientific training, they are familiar with the process of science, and how understanding changes through trial and error. In contrast, most patients usually only see the end product (ie, a drug comes to market). Discussions with patients that acknowledge uncertainty and emphasize that changes in what is known are expected and appropriate as scientific knowledge evolves could help preempt skepticism when messages are updated.
 

Why do patients with SMI need more help?

SMI as a high-risk group. Patients with SMI are part of a “tragic” epidemiologic triad of agent-host-environment¹⁵ that places them at remarkably elevated risk for COVID-19 infection and more serious complications and death when infected.¹ After age, a diagnosis of a schizophrenia spectrum disorder is the second largest predictor of mortality from COVID-19, with a 2.7-fold increase in mortality.²² This is how the elements of the triad come together: SARS-Cov-2 is a highly infectious agent affecting individuals who are vulnerable hosts because of their high frequency of medical comorbidities, including cardio­vascular disease, type 2 diabetes, and respiratory tract diseases, which are all risk factors for worse outcomes due to COVID-19.²³ In addition, SMI is associated with socioeconomic risk factors for SARS-Cov-2 infection, including poverty, homelessness, and crowded settings such as jails, group homes, hospitals, and shelters, which constitute ideal environments for high transmission of the virus.

Structural barriers to vaccination. Studies have suggested lower rates of vaccination among people with SMI for various other infectious diseases compared with the general population.¹² For example, in 1 outpatient mental health setting, influenza vaccination rates were 24% to 28%, which was lower than the national vaccination rate of 40.9% for the same influenza season (2010 to 2011).²⁴ More recently, a study in Israel examining the COVID-19 vaccination rate among >25,000 patients with schizophrenia suggested under-vaccination of this cohort. The results showed that the odds of getting the COVID-19 vaccination were significantly lower in the schizophrenia group compared with the general population (odds ratio = 0.80, 95% CI: 0.77 to 0.83).²⁵

Patients with SMI encounter considerable system-level barriers to vaccinations in general, such as reduced access to health care due to cost and a lack of transportation,¹² the digital divide given their reduced access to the internet and computers for information and scheduling,²⁶ and lack of vaccination recommendations from their PCPs.¹² Studies have also shown that patients with SMI often receive suboptimal medical care because of stigmatization and discrimination.²⁷ They also have lower rates of preventive care utilization, seeking medical services only in times of crisis and seeking mental health services more often than physical health care.^28-30

Continue to: Patients with SMI face...

Patients with SMI face additional individual challenges that impede vaccine uptake, such as lack of knowledge and awareness about the virus and vaccinations, general cognitive impairment, low digital literacy skills,³¹ low language literacy and educational attainment, baseline delusions, and negative symptoms such as apathy, avolition, and anhedonia.¹ Thus, even if they overcome the external barriers and obtain vaccine-related information, these patients may experience difficulty in understanding the content and applying this information to their personal circumstances as a result of low health literacy.

How psychiatrists can help

The concept of using mental health care sites and trained clinicians to increase medical disease prevention is not new. The rigorously tested intervention model STIRR (Screen, Test, Immunize, Reduce risk, and Refer) uses co-located nurse practitioners in community mental health centers to provide risk assessment, counseling, and blood testing for hepatitis and HIV, as well as on-site vaccinations for hepatitis to patients dually diagnosed with SMI and substance use disorders.³² Similarly, when a vaccination program was integrated into an outpatient mental health clinic offering various on-site vaccinations, vaccination rates increased by up to 25% over baseline.¹² Such public health approaches of integrating medical care at the site of mental health care, where patients with SMI are most reliably engaged, can be highly cost-effective³³ in terms of reducing disease burden among patients with SMI.

While the psychiatrist may not have the time and resources to directly follow through on all aspects of vaccinations, they can assume leadership and work with the larger team—including therapists and counselors, nurse practitioners, social workers, case managers, care coordinators, or PCPs with whom they regularly collaborate in caring for patients with SMI—to communicate what they have learned about patient hesitancies, share suggestions for future conversations to address these hesitancies, and relay what structural barriers the patient may need assistance to address.

Prioritization of patients with SMI for vaccine eligibility does not directly lead to vaccine uptake. Patients with SMI need extra support from their primary point of health care contact, namely their psychiatrists. Psychiatrists may bring a set of specialized skills uniquely suited to this moment to address vaccine hesitancy and overall lack of vaccine resources and awareness. Freudenreich et al² recently proposed “The ABCs of Successful Vaccinations” framework that psychiatrists can use in their interactions with patients to encourage vaccination by focusing on:

• attitudes towards vaccination
• barriers to vaccination
• completed vaccination series.

Understand attitudes toward vaccination. Decision-making may be an emotional and psychological experience that is informed by thoughts and feelings,³⁴ and psychiatrists are uniquely positioned to tailor messages to individual patients by using motivational interviewing and applying nudging techniques.⁸ Given the large role of the pandemic in everyday life, it would be natural to address vaccine-related concerns in the course of routine rapport-building. Table 2^19,34-38 shows example phrases of COVID-19 vaccine messages that are based on communication strategies that have demonstrated success in health behavior domains (including vaccinations).³⁹

Continue to: First, a strong recommendation...

First, a strong recommendation should be made using the presumptive approach.⁴⁰ If vaccine hesitancy is detected, psychiatrists should next attempt to understand patients’ reasoning with open-ended questions to probe vaccine-related concerns. Motivational interviewing can then be used to target the fence sitters (rather than anti-vaxxers).⁶ Psychiatrists can also communicate with therapists about the need for further follow up on patients’ hesitancies.

When assuring patients of vaccine safety and efficacy, it is helpful to explain the vaccine development process, including FDA approval, extensive clinical trials, monitoring, and the distribution process. Providing clear, transparent, accurate information about the risks and benefits of the vaccines is important, as well as monitoring misinformation and developing convincing counter messages that elicit positive emotions toward the vaccines.⁴¹ Examples of messages to counter common vaccine-related concerns and misinformation are shown in Table 3.^42-44

Know the barriers to vaccination. The role of the psychiatrist is to help patients, particularly those with SMIs, overcome logistical barriers and address hesitancy, which are both essential for vaccine uptake. Psychiatrists can help identify actual barriers (eg, transportation, digital access for information and scheduling) and perceived barriers, improve information access, and help patients obtain self-efficacy to take the actions needed to get vaccinated, particularly by collaborating with and communicating these concerns to other social services (Table 4).⁴¹

Monitor for vaccination series completion. Especially for vaccines that require more than a single dose over time, patients need more reminders, nudges, practical support, and encouragement to complete vaccination. A surprising degree of confusion regarding the timing of protection and benefit from the second COVID-19 injection (for the 2-injection vaccines) was uncovered in a recent survey of >1,000 US adults who had received their vaccinations in February 2021.⁴⁵ Attentive monitoring of vaccination series completion by psychiatrists can thus increase the likelihood that a patient will follow through (Table 4).⁴¹ This can be as simple as asking about completion of the series during appointments, but further aided by communicating to the larger care team (social workers, care managers, care coordinators) when identifying that the patient may need further assistance.

The Figure^2,6,7,19,40 summarizes the steps that psychiatrists can take to help patients get vaccinated by assessing attitudes towards vaccination (vaccine hesitancy), helping to remove barriers to vaccination, and ensuring via patient follow-up that a vaccine series is completed.

Continue to: Active involvement is key

Active involvement is key

The active involvement of psychiatrists in COVID-19 vaccination efforts can protect patients from the virus, reduce health disparities among patients with SMI, and promote herd immunity, helping to end the pandemic. Psychiatry practices can serve as ideal platforms to deliver evidence-based COVID-19 vaccine information and encourage vaccine uptake, particularly for marginalized populations.

Vaccination programs in mental health practices can even be conceptualized as a moral mandate in the spirit of addressing distributive injustice. The population management challenges of individual-level barriers and follow-through could be dramatically reduced—if not nearly eliminated—through policy-level changes that allow vaccinations to be administered in places where patients with SMI are already engaged: that is, “shots in arms” in mental health settings. As noted, some studies have shown that mental health settings can play a key role in other preventive care campaigns, such as the annual influenza and hepatitis vaccinations, and thus the incorporation of preventive care need not be limited to just COVID-19 vaccination efforts.

The COVID-19 pandemic is an opportunity to rethink the role of psychiatrists and psychiatric offices and clinics in preventive health care. The health risks and disparities of patients with SMI require the proactive involvement of psychiatrists at both the level of their individual patients and at the federal and state levels to advocate for policy changes that can benefit these populations. Overall, psychiatrists occupy a special role within the medical establishment that enables them to uniquely advocate for patients with SMI and ensure they are not forgotten during the COVID-19 pandemic.

Bottom Line

Psychiatrists could apply behavior management techniques such as motivational interviewing and nudging to address vaccine hesitancy in their patients and move them to accepting the COVID-19 vaccination. This could be particularly valuable for patients with serious mental illness, who face increased risks from COVID-19 and additional barriers to getting vaccinated.

Related Resources

• American Psychiatric Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-Coronavirus
• Baddeley M. Behavioural economics: a very short introduction. Oxford University Press; 2017.
• Centers for Disease Control and Prevention. Vaccines for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/index.html
• Chou W, Burgdorf C, Gaysynsky A, et al. COVID-19 vaccination communication: applying behavioral and social science to address vaccine hesitancy and foster vaccine confidence. National Institutes of Health. Published 2020. https://obssr.od.nih.gov/sites/obssr/files/inline-files/OBSSR_VaccineWhitePaper_FINAL_508.pdf
• Miller WR, Rollnick S. Motivational interviewing: helping people change. Guilford Press; 2012.

After more than 600,000 deaths in the United States from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several safe and effective vaccines against the virus have become available. Vaccines are the most effective preventive measure against COVID-19 and the most promising way to achieve herd immunity to end the current pandemic. However, obstacles to reaching this goal include vaccine skepticism, structural barriers, or simple inertia to get vaccinated. These challenges provide opportunities for psychiatrists to use their medical knowledge and expertise, applying behavior management techniques such as motivational interviewing and nudging to encourage their patients to get vaccinated. In particular, marginalized patients with serious mental illness (SMI), who are subject to disproportionately high rates of COVID-19 infection and more severe outcomes,¹ have much to gain if psychiatrists become involved in the COVID-19 vaccination campaign.

In this article, we define vaccine hesitancy and highlight what makes psychiatrists ideal vaccine ambassadors, given their unique skill set and longitudinal, trust-based connection with their patients. We expand on the particular vulnerabilities of patients with SMI, including structural barriers to vaccination that lead to health disparities and inequity. Finally, building on “The ABCs of successful vaccinations” framework published in Current Psychiatry March 2021,² we outline how psychiatrists can address vaccine misconceptions, employ effective communication strategies to build vaccine confidence, and help patients overcome structural barriers and get the COVID-19 vaccination. While we are currently focused on ending the COVID-19 pandemic, our broader mission as psychiatrists should be to become ambassadors for other vaccinations as well, such as the annual influenza vaccine.

What is vaccine hesitancy?

The World Health Organization (WHO) defines vaccine hesitancy as a “delay in acceptance or refusal of vaccines despite availability of vaccine services.”^3,4 Vaccine hesitancy occurs on a continuum ranging from uncertainty about accepting a vaccine to absolute refusal.^4,5 It involves a complex decision-making process driven by contextual, individual, and social influences, and vaccine-specific issues.⁴ In the “3C” model developed by the WHO Strategic Advisory Group of Experts (SAGE) Working Group, vaccine hesitancy is influenced by confidence (trust in vaccines, in the health care system, and in policy makers), complacency (lower perceived risk), and convenience (availability, affordability, accessibility, language and health literacy, appeal of vaccination program).⁴

In 2019, the WHO named vaccine hesitancy as one of the top 10 global health threats.³ Hesitancy to receive COVID-19 vaccines may be particularly high because of their rapid development. In addition, the tumultuous political environment that often featured inconsistent messaging about the virus, its dangers, and its transmission since the early days of the pandemic created widespread public confusion and doubt as scientific understandings evolved. “Anti-vaxxer” movements that completely rejected vaccine efficacy disseminated misinformation online. Followers of these movements may have such extreme overvalued ideas that any effort to persuade them otherwise with scientific evidence will accomplish very little.^6,7 Therefore, focusing on individuals who are “sitting on the fence” about getting vaccinated can be more productive because they represent a much larger group than those who adamantly refuse vaccines, and they may be more amenable to changing beliefs and behaviors.⁸

The US Census Bureau’s Household Pulse Survey asked, “How likely are you to accept the vaccine?”⁹ As of late June 2021, 11.4% of US adults reported they would “definitely not get a vaccine” or “probably not get a vaccine,” and that number increases to 16.9% when including those who are “unsure,” although there is wide geographical variability.¹⁰

A recent study in Denmark showed that willingness to receive the COVID-19 vaccine was slightly lower among patients with mental illness (84.8%) compared with the general population (89.5%).¹¹ Given the small difference, vaccine hesitancy was not considered to be a major barrier for vaccination among patients with mental illness in Denmark. This is similar to the findings of a pre-pandemic study at a community mental health clinic in the United States involving other vaccinations, which suggested that 84% of patients with SMI perceived vaccinations as safe, effective, and important.¹² In this clinic, identified barriers to vaccinations in general among patients with SMI included lack of awareness and knowledge (42.2%), accessibility (16.3%), personal cost (13.3%), fears about immunization (10.4%), and lack of recommendations by primary care providers (PCPs) (1.5%).¹²

It is critical to distinguish attitude-driven vaccine hesitancy from a lack of education and opportunity to receive a vaccine. Particularly disadvantaged communities may be mislabeled as “vaccine hesitant” when in fact they may not have the ability to be as proactive as other population groups (eg, difficulty scheduling appointments over the Internet).

Continue to: What makes psychiatrists ideal vaccine ambassadors?

What makes psychiatrists ideal vaccine ambassadors?

There are several reasons psychiatrists can be well-positioned to contribute to the success of vaccination campaigns (Table 1). These include their frequent contact with patients and their care teams, the high trust those patients have in them, and their medical expertise and skills in applied behavioral and social science techniques, including motivational interviewing and nudging. Vaccination efforts and outreach are more effective when led by the clinician with whom the patient has the most contact because resolving vaccine hesitancy is not a one-time discussion but requires ongoing communication, persistence, and consistency.¹³ Patients may contact their psychiatrists more frequently than their other clinicians, including PCPs. For this reason, psychiatrists can serve as the gateway to health care, particularly for patients with SMI.¹⁴ In addition, interruptions in nonemergency services caused by the COVID-19 pandemic may affect vaccine delivery because patients may have been unable to see their PCPs regularly during the pandemic.¹⁵

Psychiatrists’ medical expertise and their ability to develop rapport with their patients promote trust-building. Receiving credible information from a trusted source such as a patient’s psychiatrist can be impactful. A recent poll suggested that individual health care clinicians have been consistently identified as the most trusted sources for vaccine information, including for the COVID-19 vaccines.¹⁶ There is also higher trust when there is greater continuity of care both in terms of length of time the patient has known the clinician and the number of consultations,¹⁷ an inherent part of psychiatric practice. In addition, research has shown that patients trust their psychiatrists as much as they trust their general practitioners.¹⁸

Psychiatrists are experts in behavior change, promoting healthy behaviors through motivational interviewing and nudging. They also have experience with managing patients who hold overvalued ideas as well as dealing with uncertainty, given their scientific and medical training.

Motivational interviewing is a patient-centered, collaborative approach widely used by psychiatrists to treat unhealthy behaviors such as substance use. Clinicians elicit and strengthen the patient’s desire and motivation for change while respecting their autonomy. Instead of presenting persuasive facts, the clinician creates a welcoming, nonthreatening, safe environment by engaging patients in open dialogue, reflecting back the patients’ concerns with empathy, helping them realize contradictions in behavior, and supporting self-sufficiency.¹⁹ In a nonpsychiatric setting, studies have shown the effectiveness of motivational interviewing in increasing uptake of human papillomavirus vaccines and of pediatric vaccines.²⁰

Nudging, which comes from behavioral economics and psychology, underscores the importance of structuring a choice architecture in changing the way people make their everyday decisions.²¹ Nudging still gives people a choice and respects autonomy, but it leads patients to more efficient and productive decision-making. Many nudges are based around giving good “default options” because people often do not make efforts to deviate from default options. In addition, social nudges are powerful, giving people a social reference point and normalizing certain behaviors.²¹ Psychiatrists have become skilled in nudging from working with patients with varying levels of insight and cognitive capabilities. That is, they give simple choices, prompts, and frequent feedback to reinforce “good” decisions and to discourage “bad” decisions.

Continue to: Managing overvalued ideas

Managing overvalued ideas. Psychiatrists are also well-versed in having discussions with patients who hold irrational beliefs (psychosis) or overvalued ideas. For example, psychiatrists frequently manage anorexia nervosa and hypochondria, which are rooted in overvalued ideas.⁷ While psychiatrists may not be able to directly confront the overvalued ideas, they can work around such ideas while waiting for more flexible moments. Similarly, managing patients with intense emotional commitment⁷ to commonly held anti-vaccination ideas may not be much different. Psychiatrists can work around resistance until patients may be less strongly attached to those overvalued ideas in instances when other techniques, such as motivational interviewing and nudging, may be more effective.

Managing uncertainty. Psychiatrists are experts in managing “not knowing” and uncertainty. Due to their medical scientific training, they are familiar with the process of science, and how understanding changes through trial and error. In contrast, most patients usually only see the end product (ie, a drug comes to market). Discussions with patients that acknowledge uncertainty and emphasize that changes in what is known are expected and appropriate as scientific knowledge evolves could help preempt skepticism when messages are updated.
 

Why do patients with SMI need more help?

SMI as a high-risk group. Patients with SMI are part of a “tragic” epidemiologic triad of agent-host-environment¹⁵ that places them at remarkably elevated risk for COVID-19 infection and more serious complications and death when infected.¹ After age, a diagnosis of a schizophrenia spectrum disorder is the second largest predictor of mortality from COVID-19, with a 2.7-fold increase in mortality.²² This is how the elements of the triad come together: SARS-Cov-2 is a highly infectious agent affecting individuals who are vulnerable hosts because of their high frequency of medical comorbidities, including cardio­vascular disease, type 2 diabetes, and respiratory tract diseases, which are all risk factors for worse outcomes due to COVID-19.²³ In addition, SMI is associated with socioeconomic risk factors for SARS-Cov-2 infection, including poverty, homelessness, and crowded settings such as jails, group homes, hospitals, and shelters, which constitute ideal environments for high transmission of the virus.

Structural barriers to vaccination. Studies have suggested lower rates of vaccination among people with SMI for various other infectious diseases compared with the general population.¹² For example, in 1 outpatient mental health setting, influenza vaccination rates were 24% to 28%, which was lower than the national vaccination rate of 40.9% for the same influenza season (2010 to 2011).²⁴ More recently, a study in Israel examining the COVID-19 vaccination rate among >25,000 patients with schizophrenia suggested under-vaccination of this cohort. The results showed that the odds of getting the COVID-19 vaccination were significantly lower in the schizophrenia group compared with the general population (odds ratio = 0.80, 95% CI: 0.77 to 0.83).²⁵

Patients with SMI encounter considerable system-level barriers to vaccinations in general, such as reduced access to health care due to cost and a lack of transportation,¹² the digital divide given their reduced access to the internet and computers for information and scheduling,²⁶ and lack of vaccination recommendations from their PCPs.¹² Studies have also shown that patients with SMI often receive suboptimal medical care because of stigmatization and discrimination.²⁷ They also have lower rates of preventive care utilization, seeking medical services only in times of crisis and seeking mental health services more often than physical health care.^28-30

Continue to: Patients with SMI face...

Patients with SMI face additional individual challenges that impede vaccine uptake, such as lack of knowledge and awareness about the virus and vaccinations, general cognitive impairment, low digital literacy skills,³¹ low language literacy and educational attainment, baseline delusions, and negative symptoms such as apathy, avolition, and anhedonia.¹ Thus, even if they overcome the external barriers and obtain vaccine-related information, these patients may experience difficulty in understanding the content and applying this information to their personal circumstances as a result of low health literacy.

How psychiatrists can help

The concept of using mental health care sites and trained clinicians to increase medical disease prevention is not new. The rigorously tested intervention model STIRR (Screen, Test, Immunize, Reduce risk, and Refer) uses co-located nurse practitioners in community mental health centers to provide risk assessment, counseling, and blood testing for hepatitis and HIV, as well as on-site vaccinations for hepatitis to patients dually diagnosed with SMI and substance use disorders.³² Similarly, when a vaccination program was integrated into an outpatient mental health clinic offering various on-site vaccinations, vaccination rates increased by up to 25% over baseline.¹² Such public health approaches of integrating medical care at the site of mental health care, where patients with SMI are most reliably engaged, can be highly cost-effective³³ in terms of reducing disease burden among patients with SMI.

While the psychiatrist may not have the time and resources to directly follow through on all aspects of vaccinations, they can assume leadership and work with the larger team—including therapists and counselors, nurse practitioners, social workers, case managers, care coordinators, or PCPs with whom they regularly collaborate in caring for patients with SMI—to communicate what they have learned about patient hesitancies, share suggestions for future conversations to address these hesitancies, and relay what structural barriers the patient may need assistance to address.

Prioritization of patients with SMI for vaccine eligibility does not directly lead to vaccine uptake. Patients with SMI need extra support from their primary point of health care contact, namely their psychiatrists. Psychiatrists may bring a set of specialized skills uniquely suited to this moment to address vaccine hesitancy and overall lack of vaccine resources and awareness. Freudenreich et al² recently proposed “The ABCs of Successful Vaccinations” framework that psychiatrists can use in their interactions with patients to encourage vaccination by focusing on:

• attitudes towards vaccination
• barriers to vaccination
• completed vaccination series.

Understand attitudes toward vaccination. Decision-making may be an emotional and psychological experience that is informed by thoughts and feelings,³⁴ and psychiatrists are uniquely positioned to tailor messages to individual patients by using motivational interviewing and applying nudging techniques.⁸ Given the large role of the pandemic in everyday life, it would be natural to address vaccine-related concerns in the course of routine rapport-building. Table 2^19,34-38 shows example phrases of COVID-19 vaccine messages that are based on communication strategies that have demonstrated success in health behavior domains (including vaccinations).³⁹

Continue to: First, a strong recommendation...

First, a strong recommendation should be made using the presumptive approach.⁴⁰ If vaccine hesitancy is detected, psychiatrists should next attempt to understand patients’ reasoning with open-ended questions to probe vaccine-related concerns. Motivational interviewing can then be used to target the fence sitters (rather than anti-vaxxers).⁶ Psychiatrists can also communicate with therapists about the need for further follow up on patients’ hesitancies.

When assuring patients of vaccine safety and efficacy, it is helpful to explain the vaccine development process, including FDA approval, extensive clinical trials, monitoring, and the distribution process. Providing clear, transparent, accurate information about the risks and benefits of the vaccines is important, as well as monitoring misinformation and developing convincing counter messages that elicit positive emotions toward the vaccines.⁴¹ Examples of messages to counter common vaccine-related concerns and misinformation are shown in Table 3.^42-44

Know the barriers to vaccination. The role of the psychiatrist is to help patients, particularly those with SMIs, overcome logistical barriers and address hesitancy, which are both essential for vaccine uptake. Psychiatrists can help identify actual barriers (eg, transportation, digital access for information and scheduling) and perceived barriers, improve information access, and help patients obtain self-efficacy to take the actions needed to get vaccinated, particularly by collaborating with and communicating these concerns to other social services (Table 4).⁴¹

Monitor for vaccination series completion. Especially for vaccines that require more than a single dose over time, patients need more reminders, nudges, practical support, and encouragement to complete vaccination. A surprising degree of confusion regarding the timing of protection and benefit from the second COVID-19 injection (for the 2-injection vaccines) was uncovered in a recent survey of >1,000 US adults who had received their vaccinations in February 2021.⁴⁵ Attentive monitoring of vaccination series completion by psychiatrists can thus increase the likelihood that a patient will follow through (Table 4).⁴¹ This can be as simple as asking about completion of the series during appointments, but further aided by communicating to the larger care team (social workers, care managers, care coordinators) when identifying that the patient may need further assistance.

The Figure^2,6,7,19,40 summarizes the steps that psychiatrists can take to help patients get vaccinated by assessing attitudes towards vaccination (vaccine hesitancy), helping to remove barriers to vaccination, and ensuring via patient follow-up that a vaccine series is completed.

Continue to: Active involvement is key

Active involvement is key

The active involvement of psychiatrists in COVID-19 vaccination efforts can protect patients from the virus, reduce health disparities among patients with SMI, and promote herd immunity, helping to end the pandemic. Psychiatry practices can serve as ideal platforms to deliver evidence-based COVID-19 vaccine information and encourage vaccine uptake, particularly for marginalized populations.

Vaccination programs in mental health practices can even be conceptualized as a moral mandate in the spirit of addressing distributive injustice. The population management challenges of individual-level barriers and follow-through could be dramatically reduced—if not nearly eliminated—through policy-level changes that allow vaccinations to be administered in places where patients with SMI are already engaged: that is, “shots in arms” in mental health settings. As noted, some studies have shown that mental health settings can play a key role in other preventive care campaigns, such as the annual influenza and hepatitis vaccinations, and thus the incorporation of preventive care need not be limited to just COVID-19 vaccination efforts.

The COVID-19 pandemic is an opportunity to rethink the role of psychiatrists and psychiatric offices and clinics in preventive health care. The health risks and disparities of patients with SMI require the proactive involvement of psychiatrists at both the level of their individual patients and at the federal and state levels to advocate for policy changes that can benefit these populations. Overall, psychiatrists occupy a special role within the medical establishment that enables them to uniquely advocate for patients with SMI and ensure they are not forgotten during the COVID-19 pandemic.

Bottom Line

Psychiatrists could apply behavior management techniques such as motivational interviewing and nudging to address vaccine hesitancy in their patients and move them to accepting the COVID-19 vaccination. This could be particularly valuable for patients with serious mental illness, who face increased risks from COVID-19 and additional barriers to getting vaccinated.

Related Resources

• American Psychiatric Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-Coronavirus
• Baddeley M. Behavioural economics: a very short introduction. Oxford University Press; 2017.
• Centers for Disease Control and Prevention. Vaccines for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/index.html
• Chou W, Burgdorf C, Gaysynsky A, et al. COVID-19 vaccination communication: applying behavioral and social science to address vaccine hesitancy and foster vaccine confidence. National Institutes of Health. Published 2020. https://obssr.od.nih.gov/sites/obssr/files/inline-files/OBSSR_VaccineWhitePaper_FINAL_508.pdf
• Miller WR, Rollnick S. Motivational interviewing: helping people change. Guilford Press; 2012.

The Centers for Disease Control and Prevention is expected to announce in early August that new data shows people vaccinated against COVID-19 who become infected with the Delta variant can spread it and infect others, the New York Times reported on July 29.

The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.

The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the New York Times said. The bottom line is that the CDC data shows people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.

ABC News reported earlier on Jul 29 that the CDC’s updated mask guidance followed an outbreak on Cape Cod, where crowds gathered for the Fourth of July.

As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.

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

The Centers for Disease Control and Prevention is expected to announce in early August that new data shows people vaccinated against COVID-19 who become infected with the Delta variant can spread it and infect others, the New York Times reported on July 29.

The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.

The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the New York Times said. The bottom line is that the CDC data shows people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.

ABC News reported earlier on Jul 29 that the CDC’s updated mask guidance followed an outbreak on Cape Cod, where crowds gathered for the Fourth of July.

As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.

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

The Centers for Disease Control and Prevention is expected to announce in early August that new data shows people vaccinated against COVID-19 who become infected with the Delta variant can spread it and infect others, the New York Times reported on July 29.

The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.

The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the New York Times said. The bottom line is that the CDC data shows people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.

ABC News reported earlier on Jul 29 that the CDC’s updated mask guidance followed an outbreak on Cape Cod, where crowds gathered for the Fourth of July.

As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.

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

Sleep patterns may influence risk of dementia, even decades before the onset of symptoms, according to a new analysis of data from the Whitehall II cohort study.

Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.

“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.

Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.

The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
 

Multifactorial risk

Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.

Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.

Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
 

Decades of data

During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.

A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.

The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.

Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.

Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.

Dr. Sabia and Dr. Sexton have no relevant financial disclosures.

Sleep patterns may influence risk of dementia, even decades before the onset of symptoms, according to a new analysis of data from the Whitehall II cohort study.

Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.

“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.

Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.

The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
 

Multifactorial risk

Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.

Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.

Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
 

Decades of data

During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.

A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.

The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.

Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.

Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.

Dr. Sabia and Dr. Sexton have no relevant financial disclosures.

Sleep patterns may influence risk of dementia, even decades before the onset of symptoms, according to a new analysis of data from the Whitehall II cohort study.

Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.

“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.

Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.

The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
 

Multifactorial risk

Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.

Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.

Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
 

Decades of data

During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.

A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.

The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.

Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.

Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.

Dr. Sabia and Dr. Sexton have no relevant financial disclosures.

Wrong-site surgery

Florida regulators have imposed a fine and other measures on a Tampa doctor who made a crucial error prior to his patient’s testicular surgery, as a story in the Miami Herald, among other news sites, reports.

On Sept. 10, 2019, a patient referred to in state documents as “C.F.” showed up for a procedure – a varicocelectomy – that would remove the enlarged veins in his left testicle. His doctor that day was Raul Fernandez-Crespo, MD, a urologist who had been licensed to practice in Florida since April of the same year. Dr. Fernandez-Crespo completed his urology residency at the University of Puerto Rico in 2019.

Following a conversation with C.F., Dr. Fernandez-Crespo designated what he believed was the proper surgical site – his patient’s right testicle.

He then proceeded to operate, but at some point during the procedure – news accounts don’t make clear when or how he became aware of his error – he realized C.F. had actually consented to a left-testicle varicocelectomy. With his patient still sedated, Dr. Fernandez-Crespo also completed the second procedure.

His mistake came to the attention of the Department of Health, which filed an administrative complaint against the surgeon. On June 17, 2021, the department’s medical licensing body, the Florida Board of Medicine, handed down its final order about the case.

In addition to imposing a $2,500 fine on Dr. Fernandez-Crespo and issuing “a letter of concern” – a public document that can be used as evidence in any relevant future disciplinary action against him – regulators said the surgeon must reimburse $2,045.56 to the department for its case-related administrative costs; take a 5-hour CME course in risk management or attend 8 hours of board disciplinary hearings; and, finally, give a 1-hour lecture on wrong-site surgeries at a board-approved medical facility.

Before this, Dr. Fernandez-Crespo had no previous disciplinary history with the Florida Board of Medicine.
 

Huge judgment after fertility procedure goes wrong

A Connecticut couple whose fertility and prenatal care at a state university health center proved disastrous will receive millions of dollars in damages, according to a report in the Hartford Courant.

In 2014, Jean-Marie Monroe-Lynch and her husband, Aaron Lynch, went to UConn Health, in Farmington, for treatment of Jean-Marie’s infertility. Her care was overseen by the Center for Advanced Reproductive Services (CARS), a private company then under contract with UConn Health. (The contract, which ended in 2014, obligated UConn to provide CARS providers with medical malpractice coverage.)

There, Jean-Marie was inseminated with sperm from a donor who turned out to be a carrier for cytomegalovirus (CMV), the herpes virus that can cause severe birth defects, or fetal death, when contracted by a pregnant woman. The insemination resulted in a twin pregnancy, a boy and a girl. The girl, Shay, died in utero after several of her organs became infected with CMV; the boy, Joshua, was born with severe mental and physical disabilities.

In their suit, Ms. Monroe-Lynch and her husband alleged that they were never cautioned about the risks associated with using a sperm donor whose blood had tested positive for CMV antibodies. Their suit further alleged that, at the 20-week ultrasound, UConn’s prenatal team failed to detect evidence of congenital CMV infection and again failed, at the 22-week ultrasound, to properly recognize and respond to abnormal findings.

“They totally dropped the ball,” said the couple’s attorney. “If you’re a pregnant woman and contract the virus for the first time, the results can be devastating.” 

CARS disputes this conclusion, arguing that the plaintiffs failed to prove as a “matter of scientific fact” that Ms. Monroe-Lynch was infected with CMV as the result of her intrauterine insemination.

But Superior Court Judge Mark H. Taylor disagreed. In his 107-page ruling, he said that the court “agrees with the vast majority of superior courts, concluding that a physician providing obstetric care owes a direct duty to a mother to prevent harm to her child during gestation and delivery.”

Jean-Marie Monroe-Lynch and Aaron Lynch received a $37.6 million award, consisting of $24.1 million in economic damages and $13.5 million in noneconomic damages.

Their surviving child, Joshua, will reportedly require a lifetime of medical and other care. In the meantime, UConn Health vows to appeal the Superior Court’s decision.
 

COVID patient’s relative demands justice for fatal outcome

An Indiana man whose grandfather recently died after suffering a stroke is calling on state lawmakers to rethink legislation passed earlier this year to protect health care providers during the COVID-19 pandemic, according to a story reported by CBS4Indy.

Late last year, Daniel Enlow’s 83-year-old grandfather, Edward Rigney, was checked into Eskenazi Hospital, in Indianapolis. Mr. Rigney suffered from COPD and had also been diagnosed with COVID-19.

At some point during his hospitalization, medical staff attempted to place what seems to have been an arterial line in order to monitor his condition. During the procedure, or at some point shortly thereafter, an “iatrogenic air embolus” was released into his veins and caused a stroke, according to medical records and Mr. Rigney’s death certificate.

“I started asking for medical records because I wanted to know what was happening leading up to it in black and white in front of me,” said Mr. Enlow, who wished to present his evidence to a medical review panel, as required by Indiana law. The first step in this process would have been to consult with a medical malpractice attorney, but several declined to take his case.

Why? Because a pair of bills passed by Indiana legislators in early 2021 make COVID-19–related suits – even tangentially related ones – potentially difficult to take to court.

The bills raised the bar to file a medical malpractice claim in COVID-19 cases and to allow only those that involve “gross negligence or willful or wanton misconduct.”

“In the vast majority of cases, it’s impossible to prove that,” said Fred Schultz, immediate past president of the Indiana Trial Lawyers Association, who lobbied against the legislation.

The bills were never designed to offer “blanket freedom,” said GOP State Senator Aaron Freeman, sponsor of one of the bills. “If something is being used in a way that it is a complete bar to certain claims, then maybe we need to go back and look at it and open that up a little bit and make it less restrictive. I’m certainly open to having those conversations.”

Meanwhile, Mr. Enlow has vowed to keep pushing in the name of his late grandfather. The hospital’s parent company, Eskenazi Health, has declined to comment.

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

Wrong-site surgery

Florida regulators have imposed a fine and other measures on a Tampa doctor who made a crucial error prior to his patient’s testicular surgery, as a story in the Miami Herald, among other news sites, reports.

On Sept. 10, 2019, a patient referred to in state documents as “C.F.” showed up for a procedure – a varicocelectomy – that would remove the enlarged veins in his left testicle. His doctor that day was Raul Fernandez-Crespo, MD, a urologist who had been licensed to practice in Florida since April of the same year. Dr. Fernandez-Crespo completed his urology residency at the University of Puerto Rico in 2019.

Following a conversation with C.F., Dr. Fernandez-Crespo designated what he believed was the proper surgical site – his patient’s right testicle.

He then proceeded to operate, but at some point during the procedure – news accounts don’t make clear when or how he became aware of his error – he realized C.F. had actually consented to a left-testicle varicocelectomy. With his patient still sedated, Dr. Fernandez-Crespo also completed the second procedure.

His mistake came to the attention of the Department of Health, which filed an administrative complaint against the surgeon. On June 17, 2021, the department’s medical licensing body, the Florida Board of Medicine, handed down its final order about the case.

In addition to imposing a $2,500 fine on Dr. Fernandez-Crespo and issuing “a letter of concern” – a public document that can be used as evidence in any relevant future disciplinary action against him – regulators said the surgeon must reimburse $2,045.56 to the department for its case-related administrative costs; take a 5-hour CME course in risk management or attend 8 hours of board disciplinary hearings; and, finally, give a 1-hour lecture on wrong-site surgeries at a board-approved medical facility.

Before this, Dr. Fernandez-Crespo had no previous disciplinary history with the Florida Board of Medicine.
 

Huge judgment after fertility procedure goes wrong

A Connecticut couple whose fertility and prenatal care at a state university health center proved disastrous will receive millions of dollars in damages, according to a report in the Hartford Courant.

In 2014, Jean-Marie Monroe-Lynch and her husband, Aaron Lynch, went to UConn Health, in Farmington, for treatment of Jean-Marie’s infertility. Her care was overseen by the Center for Advanced Reproductive Services (CARS), a private company then under contract with UConn Health. (The contract, which ended in 2014, obligated UConn to provide CARS providers with medical malpractice coverage.)

There, Jean-Marie was inseminated with sperm from a donor who turned out to be a carrier for cytomegalovirus (CMV), the herpes virus that can cause severe birth defects, or fetal death, when contracted by a pregnant woman. The insemination resulted in a twin pregnancy, a boy and a girl. The girl, Shay, died in utero after several of her organs became infected with CMV; the boy, Joshua, was born with severe mental and physical disabilities.

In their suit, Ms. Monroe-Lynch and her husband alleged that they were never cautioned about the risks associated with using a sperm donor whose blood had tested positive for CMV antibodies. Their suit further alleged that, at the 20-week ultrasound, UConn’s prenatal team failed to detect evidence of congenital CMV infection and again failed, at the 22-week ultrasound, to properly recognize and respond to abnormal findings.

“They totally dropped the ball,” said the couple’s attorney. “If you’re a pregnant woman and contract the virus for the first time, the results can be devastating.” 

CARS disputes this conclusion, arguing that the plaintiffs failed to prove as a “matter of scientific fact” that Ms. Monroe-Lynch was infected with CMV as the result of her intrauterine insemination.

But Superior Court Judge Mark H. Taylor disagreed. In his 107-page ruling, he said that the court “agrees with the vast majority of superior courts, concluding that a physician providing obstetric care owes a direct duty to a mother to prevent harm to her child during gestation and delivery.”

Jean-Marie Monroe-Lynch and Aaron Lynch received a $37.6 million award, consisting of $24.1 million in economic damages and $13.5 million in noneconomic damages.

Their surviving child, Joshua, will reportedly require a lifetime of medical and other care. In the meantime, UConn Health vows to appeal the Superior Court’s decision.
 

COVID patient’s relative demands justice for fatal outcome

An Indiana man whose grandfather recently died after suffering a stroke is calling on state lawmakers to rethink legislation passed earlier this year to protect health care providers during the COVID-19 pandemic, according to a story reported by CBS4Indy.

Late last year, Daniel Enlow’s 83-year-old grandfather, Edward Rigney, was checked into Eskenazi Hospital, in Indianapolis. Mr. Rigney suffered from COPD and had also been diagnosed with COVID-19.

At some point during his hospitalization, medical staff attempted to place what seems to have been an arterial line in order to monitor his condition. During the procedure, or at some point shortly thereafter, an “iatrogenic air embolus” was released into his veins and caused a stroke, according to medical records and Mr. Rigney’s death certificate.

“I started asking for medical records because I wanted to know what was happening leading up to it in black and white in front of me,” said Mr. Enlow, who wished to present his evidence to a medical review panel, as required by Indiana law. The first step in this process would have been to consult with a medical malpractice attorney, but several declined to take his case.

Why? Because a pair of bills passed by Indiana legislators in early 2021 make COVID-19–related suits – even tangentially related ones – potentially difficult to take to court.

The bills raised the bar to file a medical malpractice claim in COVID-19 cases and to allow only those that involve “gross negligence or willful or wanton misconduct.”

“In the vast majority of cases, it’s impossible to prove that,” said Fred Schultz, immediate past president of the Indiana Trial Lawyers Association, who lobbied against the legislation.

The bills were never designed to offer “blanket freedom,” said GOP State Senator Aaron Freeman, sponsor of one of the bills. “If something is being used in a way that it is a complete bar to certain claims, then maybe we need to go back and look at it and open that up a little bit and make it less restrictive. I’m certainly open to having those conversations.”

Meanwhile, Mr. Enlow has vowed to keep pushing in the name of his late grandfather. The hospital’s parent company, Eskenazi Health, has declined to comment.

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

Wrong-site surgery

Florida regulators have imposed a fine and other measures on a Tampa doctor who made a crucial error prior to his patient’s testicular surgery, as a story in the Miami Herald, among other news sites, reports.

On Sept. 10, 2019, a patient referred to in state documents as “C.F.” showed up for a procedure – a varicocelectomy – that would remove the enlarged veins in his left testicle. His doctor that day was Raul Fernandez-Crespo, MD, a urologist who had been licensed to practice in Florida since April of the same year. Dr. Fernandez-Crespo completed his urology residency at the University of Puerto Rico in 2019.

Following a conversation with C.F., Dr. Fernandez-Crespo designated what he believed was the proper surgical site – his patient’s right testicle.

He then proceeded to operate, but at some point during the procedure – news accounts don’t make clear when or how he became aware of his error – he realized C.F. had actually consented to a left-testicle varicocelectomy. With his patient still sedated, Dr. Fernandez-Crespo also completed the second procedure.

His mistake came to the attention of the Department of Health, which filed an administrative complaint against the surgeon. On June 17, 2021, the department’s medical licensing body, the Florida Board of Medicine, handed down its final order about the case.

In addition to imposing a $2,500 fine on Dr. Fernandez-Crespo and issuing “a letter of concern” – a public document that can be used as evidence in any relevant future disciplinary action against him – regulators said the surgeon must reimburse $2,045.56 to the department for its case-related administrative costs; take a 5-hour CME course in risk management or attend 8 hours of board disciplinary hearings; and, finally, give a 1-hour lecture on wrong-site surgeries at a board-approved medical facility.

Before this, Dr. Fernandez-Crespo had no previous disciplinary history with the Florida Board of Medicine.
 

Huge judgment after fertility procedure goes wrong

A Connecticut couple whose fertility and prenatal care at a state university health center proved disastrous will receive millions of dollars in damages, according to a report in the Hartford Courant.

In 2014, Jean-Marie Monroe-Lynch and her husband, Aaron Lynch, went to UConn Health, in Farmington, for treatment of Jean-Marie’s infertility. Her care was overseen by the Center for Advanced Reproductive Services (CARS), a private company then under contract with UConn Health. (The contract, which ended in 2014, obligated UConn to provide CARS providers with medical malpractice coverage.)

There, Jean-Marie was inseminated with sperm from a donor who turned out to be a carrier for cytomegalovirus (CMV), the herpes virus that can cause severe birth defects, or fetal death, when contracted by a pregnant woman. The insemination resulted in a twin pregnancy, a boy and a girl. The girl, Shay, died in utero after several of her organs became infected with CMV; the boy, Joshua, was born with severe mental and physical disabilities.

In their suit, Ms. Monroe-Lynch and her husband alleged that they were never cautioned about the risks associated with using a sperm donor whose blood had tested positive for CMV antibodies. Their suit further alleged that, at the 20-week ultrasound, UConn’s prenatal team failed to detect evidence of congenital CMV infection and again failed, at the 22-week ultrasound, to properly recognize and respond to abnormal findings.

“They totally dropped the ball,” said the couple’s attorney. “If you’re a pregnant woman and contract the virus for the first time, the results can be devastating.” 

CARS disputes this conclusion, arguing that the plaintiffs failed to prove as a “matter of scientific fact” that Ms. Monroe-Lynch was infected with CMV as the result of her intrauterine insemination.

But Superior Court Judge Mark H. Taylor disagreed. In his 107-page ruling, he said that the court “agrees with the vast majority of superior courts, concluding that a physician providing obstetric care owes a direct duty to a mother to prevent harm to her child during gestation and delivery.”

Jean-Marie Monroe-Lynch and Aaron Lynch received a $37.6 million award, consisting of $24.1 million in economic damages and $13.5 million in noneconomic damages.

Their surviving child, Joshua, will reportedly require a lifetime of medical and other care. In the meantime, UConn Health vows to appeal the Superior Court’s decision.
 

COVID patient’s relative demands justice for fatal outcome

An Indiana man whose grandfather recently died after suffering a stroke is calling on state lawmakers to rethink legislation passed earlier this year to protect health care providers during the COVID-19 pandemic, according to a story reported by CBS4Indy.

Late last year, Daniel Enlow’s 83-year-old grandfather, Edward Rigney, was checked into Eskenazi Hospital, in Indianapolis. Mr. Rigney suffered from COPD and had also been diagnosed with COVID-19.

At some point during his hospitalization, medical staff attempted to place what seems to have been an arterial line in order to monitor his condition. During the procedure, or at some point shortly thereafter, an “iatrogenic air embolus” was released into his veins and caused a stroke, according to medical records and Mr. Rigney’s death certificate.

“I started asking for medical records because I wanted to know what was happening leading up to it in black and white in front of me,” said Mr. Enlow, who wished to present his evidence to a medical review panel, as required by Indiana law. The first step in this process would have been to consult with a medical malpractice attorney, but several declined to take his case.

Why? Because a pair of bills passed by Indiana legislators in early 2021 make COVID-19–related suits – even tangentially related ones – potentially difficult to take to court.

The bills raised the bar to file a medical malpractice claim in COVID-19 cases and to allow only those that involve “gross negligence or willful or wanton misconduct.”

“In the vast majority of cases, it’s impossible to prove that,” said Fred Schultz, immediate past president of the Indiana Trial Lawyers Association, who lobbied against the legislation.

The bills were never designed to offer “blanket freedom,” said GOP State Senator Aaron Freeman, sponsor of one of the bills. “If something is being used in a way that it is a complete bar to certain claims, then maybe we need to go back and look at it and open that up a little bit and make it less restrictive. I’m certainly open to having those conversations.”

Meanwhile, Mr. Enlow has vowed to keep pushing in the name of his late grandfather. The hospital’s parent company, Eskenazi Health, has declined to comment.

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

A case report describes a novel helmet device that generates a noninvasive oscillating magnetic field and that shrunk a glioblastoma tumor by about a third.

This is the first time that the wearable Oncomagnetic device was tried with a patient.

The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.

A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.

The case study was published online on July 22, 2021, in Frontiers in Oncology.

“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”

The team is now treating several patients with glioblastoma under compassionate use.

In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
 

Oscillating magnetic fields

The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.

It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.

Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.

Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
 

Most common brain cancer in adults

Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.

“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
 

Out of the box

Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.

“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.

“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”

The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.

In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.

However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
 

Exciting possibilities

The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.

The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.

Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.

Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.

Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.

“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.

He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.

The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.

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

A case report describes a novel helmet device that generates a noninvasive oscillating magnetic field and that shrunk a glioblastoma tumor by about a third.

This is the first time that the wearable Oncomagnetic device was tried with a patient.

The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.

A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.

The case study was published online on July 22, 2021, in Frontiers in Oncology.

“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”

The team is now treating several patients with glioblastoma under compassionate use.

In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
 

Oscillating magnetic fields

The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.

It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.

Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.

Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
 

Most common brain cancer in adults

Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.

“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
 

Out of the box

Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.

“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.

“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”

The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.

In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.

However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
 

Exciting possibilities

The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.

The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.

Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.

Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.

Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.

“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.

He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.

The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.

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

A case report describes a novel helmet device that generates a noninvasive oscillating magnetic field and that shrunk a glioblastoma tumor by about a third.

This is the first time that the wearable Oncomagnetic device was tried with a patient.

The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.

A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.

The case study was published online on July 22, 2021, in Frontiers in Oncology.

“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”

The team is now treating several patients with glioblastoma under compassionate use.

In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
 

Oscillating magnetic fields

The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.

It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.

Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.

Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
 

Most common brain cancer in adults

Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.

“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
 

Out of the box

Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.

“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.

“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”

The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.

In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.

However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
 

Exciting possibilities

The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.

The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.

Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.

Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.

Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.

“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.

He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.

The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.

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

The U.S. Food and Drug Administration has issued a safety alert regarding an increased risk of death associated with Pepaxto (melphalan flufenamide) used in patients with multiple myeloma participating in the ongoing OCEAN clinical trial.

The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.

Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.

The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.

Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”

The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
 

Accelerated approval data

Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.

Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
 

Confirmatory trial data

The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.

The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.

“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.

The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.

Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.

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

The U.S. Food and Drug Administration has issued a safety alert regarding an increased risk of death associated with Pepaxto (melphalan flufenamide) used in patients with multiple myeloma participating in the ongoing OCEAN clinical trial.

The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.

Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.

The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.

Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”

The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
 

Accelerated approval data

Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.

Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
 

Confirmatory trial data

The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.

The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.

“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.

The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.

Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.

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

The U.S. Food and Drug Administration has issued a safety alert regarding an increased risk of death associated with Pepaxto (melphalan flufenamide) used in patients with multiple myeloma participating in the ongoing OCEAN clinical trial.

The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.

Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.

The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.

Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”

The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
 

Accelerated approval data

Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.

Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
 

Confirmatory trial data

The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.

The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.

“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.

The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.

Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.

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

Clinical trials underway across the United States are exploring the use of robotic surgical devices for nipple-sparing mastectomy, but are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning from the Food and Drug Administration that those outcomes are important.

The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.

The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.

The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.

In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.

Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.

However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.

Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.

Importantly, none of the studies is a randomized trial; all have single arms.

That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.

“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.

As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”

In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
 

Not looking at the right outcomes

“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.

“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.

The current U.S. trials are “totally inappropriate,” he said.

Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.  

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.

What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.  

Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
 

Safety concerns with robotic mastectomy

Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.

That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.

But therein also lies a safety concern, she asserted.

The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”

Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”

Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.

Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
 

In defense of single-arm trials

“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.

Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.

The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.

The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.

“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.

But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”

Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
 

Prophylactic use is also a cancer surgery

Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.

Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.

“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.  

Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.

Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.

It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.

“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.

The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
 

Surgeons only get one body

Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.

However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.

Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.

One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.

Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.

“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.

When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”

Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.

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

Clinical trials underway across the United States are exploring the use of robotic surgical devices for nipple-sparing mastectomy, but are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning from the Food and Drug Administration that those outcomes are important.

The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.

The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.

The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.

In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.

Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.

However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.

Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.

Importantly, none of the studies is a randomized trial; all have single arms.

That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.

“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.

As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”

In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
 

Not looking at the right outcomes

“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.

“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.

The current U.S. trials are “totally inappropriate,” he said.

Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.  

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.

What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.  

Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
 

Safety concerns with robotic mastectomy

Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.

That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.

But therein also lies a safety concern, she asserted.

The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”

Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”

Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.

Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
 

In defense of single-arm trials

“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.

Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.

The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.

The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.

“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.

But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”

Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
 

Prophylactic use is also a cancer surgery

Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.

Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.

“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.  

Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.

Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.

It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.

“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.

The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
 

Surgeons only get one body

Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.

However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.

Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.

One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.

Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.

“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.

When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”

Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.

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

Clinical trials underway across the United States are exploring the use of robotic surgical devices for nipple-sparing mastectomy, but are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning from the Food and Drug Administration that those outcomes are important.

The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.

The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.

The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.

In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.

Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.

However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.

Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.

Importantly, none of the studies is a randomized trial; all have single arms.

That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.

“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.

As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”

In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
 

Not looking at the right outcomes

“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.

“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.

The current U.S. trials are “totally inappropriate,” he said.

Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.  

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.

What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.  

Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
 

Safety concerns with robotic mastectomy

Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.

That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.

But therein also lies a safety concern, she asserted.

The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”

Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”

Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.

Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
 

In defense of single-arm trials

“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.

Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.

The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.

The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.

“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.

But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”

Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
 

Prophylactic use is also a cancer surgery

Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.

Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.

“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.  

Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.

Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.

It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.

“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.

The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
 

Surgeons only get one body

Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.

However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.

Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.

One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.

Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.

“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.

When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”

Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.

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

The U.S. Food and Drug Administration has expanded the indication for rimegepant (Nurtec ODT, Biohaven) to include prevention of migraine in adults. Last year, rimegepant became the first calcitonin gene-related peptide (CGRP) receptor antagonist, available in a fast-acting orally disintegrating tablet, to be approved for the acute treatment of migraine with or without aura in adults.

Rimegepant is currently the only migraine medication approved to both treat acute migraine attacks and help prevent future migraine attacks.

The new indication allows for use of rimegepant for preventive treatment in adults with episodic migraine (more than 15 migraine days per month). Rimegepant may be used for up to 18 doses per month, which includes both acute and preventive therapy.

In a phase 2/3 study, oral rimegepant was superior to placebo in reducing monthly migraine days. About half of adults who took rimegepant experienced a 50% or greater reduction in the number of days of moderate to severe migraines per month.

The most common adverse effects of rimegepant therapy were nausea (2.7%) and stomach pain or indigestion (2.4%).

The FDA approval of rimegepant for the preventive treatment of migraine, along with its acute treatment indication, is “one of the most ground-breaking things to happen to migraine treatment in my 40 years of practicing headache medicine,” Peter J. Goadsby, MD, PhD, an investigator in the prevention study, said in a company news release.   

“To have one medication patients can use to treat and prevent migraine will likely change the treatment paradigm for many of the millions of people who live with migraine,” said Dr. Goadsby, professor of neurology, University of California, Los Angeles and King’s College, London.

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

The U.S. Food and Drug Administration has expanded the indication for rimegepant (Nurtec ODT, Biohaven) to include prevention of migraine in adults. Last year, rimegepant became the first calcitonin gene-related peptide (CGRP) receptor antagonist, available in a fast-acting orally disintegrating tablet, to be approved for the acute treatment of migraine with or without aura in adults.

Rimegepant is currently the only migraine medication approved to both treat acute migraine attacks and help prevent future migraine attacks.

The new indication allows for use of rimegepant for preventive treatment in adults with episodic migraine (more than 15 migraine days per month). Rimegepant may be used for up to 18 doses per month, which includes both acute and preventive therapy.

In a phase 2/3 study, oral rimegepant was superior to placebo in reducing monthly migraine days. About half of adults who took rimegepant experienced a 50% or greater reduction in the number of days of moderate to severe migraines per month.

The most common adverse effects of rimegepant therapy were nausea (2.7%) and stomach pain or indigestion (2.4%).

The FDA approval of rimegepant for the preventive treatment of migraine, along with its acute treatment indication, is “one of the most ground-breaking things to happen to migraine treatment in my 40 years of practicing headache medicine,” Peter J. Goadsby, MD, PhD, an investigator in the prevention study, said in a company news release.   

“To have one medication patients can use to treat and prevent migraine will likely change the treatment paradigm for many of the millions of people who live with migraine,” said Dr. Goadsby, professor of neurology, University of California, Los Angeles and King’s College, London.

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

The U.S. Food and Drug Administration has expanded the indication for rimegepant (Nurtec ODT, Biohaven) to include prevention of migraine in adults. Last year, rimegepant became the first calcitonin gene-related peptide (CGRP) receptor antagonist, available in a fast-acting orally disintegrating tablet, to be approved for the acute treatment of migraine with or without aura in adults.

Rimegepant is currently the only migraine medication approved to both treat acute migraine attacks and help prevent future migraine attacks.

The new indication allows for use of rimegepant for preventive treatment in adults with episodic migraine (more than 15 migraine days per month). Rimegepant may be used for up to 18 doses per month, which includes both acute and preventive therapy.

In a phase 2/3 study, oral rimegepant was superior to placebo in reducing monthly migraine days. About half of adults who took rimegepant experienced a 50% or greater reduction in the number of days of moderate to severe migraines per month.

The most common adverse effects of rimegepant therapy were nausea (2.7%) and stomach pain or indigestion (2.4%).

The FDA approval of rimegepant for the preventive treatment of migraine, along with its acute treatment indication, is “one of the most ground-breaking things to happen to migraine treatment in my 40 years of practicing headache medicine,” Peter J. Goadsby, MD, PhD, an investigator in the prevention study, said in a company news release.   

“To have one medication patients can use to treat and prevent migraine will likely change the treatment paradigm for many of the millions of people who live with migraine,” said Dr. Goadsby, professor of neurology, University of California, Los Angeles and King’s College, London.

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

The goal of treating medication overuse headache is obvious: ceasing overuse of the medication in question in an effort to return to a headache pattern that is episodic and better managed. Although guidelines suggest withdrawal of the overused medication and initiating preventive treatment, there is debate about this approach versus withdrawal alone or preventive treatment without ceasing the overused medication. A recently published randomized trial from Carlsen and colleagues evaluated 3 treatment methods: 1) withdrawal plus preventive treatment; 2) preventive treatment only; and 3) withdrawal followed by optional preventive treatment 2 months after withdrawal. Investigators found all 3 approaches effective, but participants who underwent withdrawal plus preventive care saw their headache days reduced by 12.3 days, versus 9.9 days in the preventive-only group and 8.5 days in the withdrawal/optional preventive follow-up treatment contingent. No statistically significant differences were seen between the groups in terms of migraine days, days with short-term medication use, and headache pain intensity.

Particularly noteworthy was the finding that individuals treated with withdrawal plus preventive treatment were significantly more likely to achieve remission. Specifically, nearly 75% returned to experiencing episodic headache, compared with 60% in the preventive group and 42% in the withdrawal contingent. Nearly all (97%) of those on the withdrawal plus preventive regimen were cured of medication overuse headache, versus 90% (withdrawal) and 74% (preventive).

The bottom line: Individuals undergoing withdrawal plus preventive treatment were 30% more likely to be cured of medication overuse headache. Thus, it appears that detoxification is key.

Or is it?

On the one hand…

In studies, withdrawal from the offending medication is linked with substantial improvement in headache days. Additionally, individuals who previously responded poorly to preventive treatment fared better with such treatment after detoxification.

When treating medication overuse headache using the detoxification and preventive care approach, Sun-Edelstein and colleagues outline these important steps:

• Educate your patients and their family/caregivers about the detoxification process
• Wean patient off the offending medication with a goal of complete detoxification
• Initiate preventive medical therapy or behavioral/non-drug strategies
• Establish clear limits on acute medication intake
• Arrange for regular follow-up to minimize or prevent relapse

While on the other hand…

Even though guidelines recommend detoxification, there is data supporting the concept of initiating preventive treatment without detoxification. A randomized, double-blind, placebo-controlled trial by Mei and colleagues found that 100 mg per day of topiramate led to a significant reduction in headache days and average amount of acute medication intake, versus placebo. However, treatment completion rates were low, leading Sun-Edelstein and colleagues to surmise that topiramate without detoxification would probably not have had a high success rate in practice.

Meanwhile, onabotulinumtoxin A was found in the PREEMPT trials conducted by Dodick and colleagues to reduce the number of headache days, migraine days, and moderate/severe headache days, compared with placebo, at week 24. Disappointingly, researchers found that acute medication frequency was not reduced in the overall treatment group, but they did note a significant reduction in the subgroup that was taking triptans. Moreover, a follow-up analysis by Aurora and colleagues involving 32 weeks of open-label treatment with onabotulinumtoxin A following the 24-week randomized study revealed significant reductions in acute headache days at 56 weeks.

Using anti-CGRPs without acute medication withdrawal

More recently, strong evidence is emerging about the value of using anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies without acute medication withdrawal. The findings involve 4 anti-CGRP medications.

Erenumab: A subgroup analysis of a randomized, double-blind, placebo-controlled parallel-group trial by Tepper and colleagues showed that erenumab reduced frequency of migraine at 3 months in participants with chronic migraine and medication overuse. Patients receiving either 70 or 140 mg of erenumab saw their migraine frequency reduced by an average of 6.6 days, versus 3.5 days in the placebo group. 

Additionally, a significantly greater number of patients in the treatment groups stopped overusing medication, and did so early, which led to improved patient-reported outcomes. Acute migraine-specific medication treatment days were reduced by an average of 5.4 days in the 70 mg group, 4.9 days in the 140 mg contingent, and 2.9 days in those who received placebo.

Overall, consistent improvement in measures of impact, disability and health-related quality of life were seen in individuals’ treatment with erenumab.

Galcanezumab: A post-hoc analysis of pooled data from the phase 3 EVOLVE-1 and EVOLVE-2 studies, as well as the phase 3 REGAIN trial found that in participants with medication overuse, 120 mg and 240 mg doses of galcanezumab cut the number of average migraine days and decreased medication overuse. Average migraine days were lowered in EVOLVE participants by 6.26 days in the 120 mg group, 5.77 days in the 240 mg contingent, and 2.71 in those who received placebo. In REGAIN, these numbers were 4.78, 4.51, and 2.25, respectively. Average monthly medication use rates in EVOLVE were 6.2%, 7.9%, and 15.9%, respectively; in REGAIN they were 24.3%, 23.1%, and 40.6%, respectively.

Notably, though the study demonstrated galcanezumab’s efficacy in those with and without medication overuse, improvement was more pronounced in patients with medication overuse.

Fremanezumab: In an analysis by Silberstein and colleagues, significantly more patients who received quarterly or monthly injections of fremanezumab reported no medication overuse during the 3-month study, versus placebo. Specifically, 61% of participants who received monthly injections of fremanezumab and 55% of those who took quarterly injections reported no medication overuse. Among those receiving placebo, only 46% reverted to no overuse. The effect was seen as early as week 4. Additionally, among patients with medication overuse at baseline, the number of days with acute medication use was significantly lower in the treatment groups versus placebo—1.8 days lower in the quarterly group and 2.8 days in the monthly contingent.

A subsequent post-hoc analysis presented at the 2019 American Headache Society (AHS) Annual Scientific Meeting showed that the benefits were sustained over time and the medication was effective in difficult cases. Continued treatment with either quarterly or monthly dosing resulted in a reduced number of headache days, acute medication overuse headache, and headache-related disability, compared with baseline measures. Notably, about 6 in every 10 individuals with medication overuse at baseline who received fremanezumab reverted to no acute medication overuse at 6 months. This effect was maintained through 1 year of treatment.

Eptinezumab: In PROMISE-2, a post-hoc analysis of the phase 3 trials evaluating quarterly IV infusions of eptinezumab 100 mg and 300 mg, Lipton and colleagues reported that participants with chronic migraine and medication overuse experienced greater reductions in monthly migraine days during weeks 1 through 12, versus placebo (100 mg, 7.7 days; 300 mg, 8.2 days; placebo, 5.6 days). Benefits, seen as early as the day after dosing, were generally maintained or improved over 24 weeks.

Acute care medication use was reduced by about 50% in the treatment group versus roughly 25% in the placebo contingent. Most encouraging was the finding that about one-third of individuals in the treatment cohort experienced 6 months without medication overuse and below the chronic migraine diagnostic threshold; only 10% of patients who received placebo resolved in this way. Consistent improvement across patient-reported outcomes was also observed in the treatment group versus placebo.

While the studies involving topiramate, onabotulinumtoxin A, and the anti-CGRP monoclonal antibodies suggest that preventive treatment alone may effectively treat acute medical overuse and medication overuse headache, it is the data behind the anti-CGRP treatments that seem to be most compelling and causing conventional thinking to be challenged. These medications appear to be able to convert individuals with chronic migraine and medication overuse, out of overuse and back to episodic migraine. Moreover, results show they may be able to reduce acute medication use in episodic migraine, which reduces the risk of the headache sufferer transforming to chronic migraine. It is worth considering this approach in patients’ overuse acute care medication, as well as those in whom discontinuation may otherwise prove difficult without concurrent preventive treatment.

The emerging role of gepants

Availability of the so-called “gepants”—small molecule CGRP receptor agonists—is shedding additional light on management of medication overuse headache and pointing to the future. Gepants—which include ubrogepant, rimegepant, and atogepant—have been shown in early data to have a preventive effect when used regularly. Thus, it is much less likely that their use will lead to excess use and medication overuse headache.

Preclinical data demonstrated that continued use of ubrogepant does not appear to produce early or latent trigeminal sensory sensitization. Meanwhile, rimegepant, when used every other day, and as needed for acute treatment of migraine in individuals suffering from moderate-to-high frequency episodic migraine, resulted in reductions in monthly migraine days. The preventive effects appear to be rapid and sustained. And in a phase 3 trial, atogepant demonstrated efficacy at doses of 10 mg, 30 mg, and 60 mg twice a day, compared with placebo over 12 weeks.

It is important to note that the link between the gepants and medication overuse and medication overuse headache have not yet been studied. Still, it is encouraging to see that migraine frequency improves and medication use days are reduced when gepants are taken preventively. Thus, gepants could emerge as a preferred approach for acute or preventive treatment in individuals who have or are at risk of developing medication overuse headache.

The goal of treating medication overuse headache is obvious: ceasing overuse of the medication in question in an effort to return to a headache pattern that is episodic and better managed. Although guidelines suggest withdrawal of the overused medication and initiating preventive treatment, there is debate about this approach versus withdrawal alone or preventive treatment without ceasing the overused medication. A recently published randomized trial from Carlsen and colleagues evaluated 3 treatment methods: 1) withdrawal plus preventive treatment; 2) preventive treatment only; and 3) withdrawal followed by optional preventive treatment 2 months after withdrawal. Investigators found all 3 approaches effective, but participants who underwent withdrawal plus preventive care saw their headache days reduced by 12.3 days, versus 9.9 days in the preventive-only group and 8.5 days in the withdrawal/optional preventive follow-up treatment contingent. No statistically significant differences were seen between the groups in terms of migraine days, days with short-term medication use, and headache pain intensity.

Particularly noteworthy was the finding that individuals treated with withdrawal plus preventive treatment were significantly more likely to achieve remission. Specifically, nearly 75% returned to experiencing episodic headache, compared with 60% in the preventive group and 42% in the withdrawal contingent. Nearly all (97%) of those on the withdrawal plus preventive regimen were cured of medication overuse headache, versus 90% (withdrawal) and 74% (preventive).

The bottom line: Individuals undergoing withdrawal plus preventive treatment were 30% more likely to be cured of medication overuse headache. Thus, it appears that detoxification is key.

Or is it?

On the one hand…

In studies, withdrawal from the offending medication is linked with substantial improvement in headache days. Additionally, individuals who previously responded poorly to preventive treatment fared better with such treatment after detoxification.

When treating medication overuse headache using the detoxification and preventive care approach, Sun-Edelstein and colleagues outline these important steps:

• Educate your patients and their family/caregivers about the detoxification process
• Wean patient off the offending medication with a goal of complete detoxification
• Initiate preventive medical therapy or behavioral/non-drug strategies
• Establish clear limits on acute medication intake
• Arrange for regular follow-up to minimize or prevent relapse

While on the other hand…

Even though guidelines recommend detoxification, there is data supporting the concept of initiating preventive treatment without detoxification. A randomized, double-blind, placebo-controlled trial by Mei and colleagues found that 100 mg per day of topiramate led to a significant reduction in headache days and average amount of acute medication intake, versus placebo. However, treatment completion rates were low, leading Sun-Edelstein and colleagues to surmise that topiramate without detoxification would probably not have had a high success rate in practice.

Meanwhile, onabotulinumtoxin A was found in the PREEMPT trials conducted by Dodick and colleagues to reduce the number of headache days, migraine days, and moderate/severe headache days, compared with placebo, at week 24. Disappointingly, researchers found that acute medication frequency was not reduced in the overall treatment group, but they did note a significant reduction in the subgroup that was taking triptans. Moreover, a follow-up analysis by Aurora and colleagues involving 32 weeks of open-label treatment with onabotulinumtoxin A following the 24-week randomized study revealed significant reductions in acute headache days at 56 weeks.

Using anti-CGRPs without acute medication withdrawal

More recently, strong evidence is emerging about the value of using anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies without acute medication withdrawal. The findings involve 4 anti-CGRP medications.

Erenumab: A subgroup analysis of a randomized, double-blind, placebo-controlled parallel-group trial by Tepper and colleagues showed that erenumab reduced frequency of migraine at 3 months in participants with chronic migraine and medication overuse. Patients receiving either 70 or 140 mg of erenumab saw their migraine frequency reduced by an average of 6.6 days, versus 3.5 days in the placebo group. 

Additionally, a significantly greater number of patients in the treatment groups stopped overusing medication, and did so early, which led to improved patient-reported outcomes. Acute migraine-specific medication treatment days were reduced by an average of 5.4 days in the 70 mg group, 4.9 days in the 140 mg contingent, and 2.9 days in those who received placebo.

Overall, consistent improvement in measures of impact, disability and health-related quality of life were seen in individuals’ treatment with erenumab.

Galcanezumab: A post-hoc analysis of pooled data from the phase 3 EVOLVE-1 and EVOLVE-2 studies, as well as the phase 3 REGAIN trial found that in participants with medication overuse, 120 mg and 240 mg doses of galcanezumab cut the number of average migraine days and decreased medication overuse. Average migraine days were lowered in EVOLVE participants by 6.26 days in the 120 mg group, 5.77 days in the 240 mg contingent, and 2.71 in those who received placebo. In REGAIN, these numbers were 4.78, 4.51, and 2.25, respectively. Average monthly medication use rates in EVOLVE were 6.2%, 7.9%, and 15.9%, respectively; in REGAIN they were 24.3%, 23.1%, and 40.6%, respectively.

Notably, though the study demonstrated galcanezumab’s efficacy in those with and without medication overuse, improvement was more pronounced in patients with medication overuse.

Fremanezumab: In an analysis by Silberstein and colleagues, significantly more patients who received quarterly or monthly injections of fremanezumab reported no medication overuse during the 3-month study, versus placebo. Specifically, 61% of participants who received monthly injections of fremanezumab and 55% of those who took quarterly injections reported no medication overuse. Among those receiving placebo, only 46% reverted to no overuse. The effect was seen as early as week 4. Additionally, among patients with medication overuse at baseline, the number of days with acute medication use was significantly lower in the treatment groups versus placebo—1.8 days lower in the quarterly group and 2.8 days in the monthly contingent.

A subsequent post-hoc analysis presented at the 2019 American Headache Society (AHS) Annual Scientific Meeting showed that the benefits were sustained over time and the medication was effective in difficult cases. Continued treatment with either quarterly or monthly dosing resulted in a reduced number of headache days, acute medication overuse headache, and headache-related disability, compared with baseline measures. Notably, about 6 in every 10 individuals with medication overuse at baseline who received fremanezumab reverted to no acute medication overuse at 6 months. This effect was maintained through 1 year of treatment.

Eptinezumab: In PROMISE-2, a post-hoc analysis of the phase 3 trials evaluating quarterly IV infusions of eptinezumab 100 mg and 300 mg, Lipton and colleagues reported that participants with chronic migraine and medication overuse experienced greater reductions in monthly migraine days during weeks 1 through 12, versus placebo (100 mg, 7.7 days; 300 mg, 8.2 days; placebo, 5.6 days). Benefits, seen as early as the day after dosing, were generally maintained or improved over 24 weeks.

Acute care medication use was reduced by about 50% in the treatment group versus roughly 25% in the placebo contingent. Most encouraging was the finding that about one-third of individuals in the treatment cohort experienced 6 months without medication overuse and below the chronic migraine diagnostic threshold; only 10% of patients who received placebo resolved in this way. Consistent improvement across patient-reported outcomes was also observed in the treatment group versus placebo.

While the studies involving topiramate, onabotulinumtoxin A, and the anti-CGRP monoclonal antibodies suggest that preventive treatment alone may effectively treat acute medical overuse and medication overuse headache, it is the data behind the anti-CGRP treatments that seem to be most compelling and causing conventional thinking to be challenged. These medications appear to be able to convert individuals with chronic migraine and medication overuse, out of overuse and back to episodic migraine. Moreover, results show they may be able to reduce acute medication use in episodic migraine, which reduces the risk of the headache sufferer transforming to chronic migraine. It is worth considering this approach in patients’ overuse acute care medication, as well as those in whom discontinuation may otherwise prove difficult without concurrent preventive treatment.

The emerging role of gepants

Availability of the so-called “gepants”—small molecule CGRP receptor agonists—is shedding additional light on management of medication overuse headache and pointing to the future. Gepants—which include ubrogepant, rimegepant, and atogepant—have been shown in early data to have a preventive effect when used regularly. Thus, it is much less likely that their use will lead to excess use and medication overuse headache.

Preclinical data demonstrated that continued use of ubrogepant does not appear to produce early or latent trigeminal sensory sensitization. Meanwhile, rimegepant, when used every other day, and as needed for acute treatment of migraine in individuals suffering from moderate-to-high frequency episodic migraine, resulted in reductions in monthly migraine days. The preventive effects appear to be rapid and sustained. And in a phase 3 trial, atogepant demonstrated efficacy at doses of 10 mg, 30 mg, and 60 mg twice a day, compared with placebo over 12 weeks.

It is important to note that the link between the gepants and medication overuse and medication overuse headache have not yet been studied. Still, it is encouraging to see that migraine frequency improves and medication use days are reduced when gepants are taken preventively. Thus, gepants could emerge as a preferred approach for acute or preventive treatment in individuals who have or are at risk of developing medication overuse headache.

The goal of treating medication overuse headache is obvious: ceasing overuse of the medication in question in an effort to return to a headache pattern that is episodic and better managed. Although guidelines suggest withdrawal of the overused medication and initiating preventive treatment, there is debate about this approach versus withdrawal alone or preventive treatment without ceasing the overused medication. A recently published randomized trial from Carlsen and colleagues evaluated 3 treatment methods: 1) withdrawal plus preventive treatment; 2) preventive treatment only; and 3) withdrawal followed by optional preventive treatment 2 months after withdrawal. Investigators found all 3 approaches effective, but participants who underwent withdrawal plus preventive care saw their headache days reduced by 12.3 days, versus 9.9 days in the preventive-only group and 8.5 days in the withdrawal/optional preventive follow-up treatment contingent. No statistically significant differences were seen between the groups in terms of migraine days, days with short-term medication use, and headache pain intensity.

Particularly noteworthy was the finding that individuals treated with withdrawal plus preventive treatment were significantly more likely to achieve remission. Specifically, nearly 75% returned to experiencing episodic headache, compared with 60% in the preventive group and 42% in the withdrawal contingent. Nearly all (97%) of those on the withdrawal plus preventive regimen were cured of medication overuse headache, versus 90% (withdrawal) and 74% (preventive).

The bottom line: Individuals undergoing withdrawal plus preventive treatment were 30% more likely to be cured of medication overuse headache. Thus, it appears that detoxification is key.

Or is it?

On the one hand…

In studies, withdrawal from the offending medication is linked with substantial improvement in headache days. Additionally, individuals who previously responded poorly to preventive treatment fared better with such treatment after detoxification.

When treating medication overuse headache using the detoxification and preventive care approach, Sun-Edelstein and colleagues outline these important steps:

• Educate your patients and their family/caregivers about the detoxification process
• Wean patient off the offending medication with a goal of complete detoxification
• Initiate preventive medical therapy or behavioral/non-drug strategies
• Establish clear limits on acute medication intake
• Arrange for regular follow-up to minimize or prevent relapse

While on the other hand…

Even though guidelines recommend detoxification, there is data supporting the concept of initiating preventive treatment without detoxification. A randomized, double-blind, placebo-controlled trial by Mei and colleagues found that 100 mg per day of topiramate led to a significant reduction in headache days and average amount of acute medication intake, versus placebo. However, treatment completion rates were low, leading Sun-Edelstein and colleagues to surmise that topiramate without detoxification would probably not have had a high success rate in practice.

Meanwhile, onabotulinumtoxin A was found in the PREEMPT trials conducted by Dodick and colleagues to reduce the number of headache days, migraine days, and moderate/severe headache days, compared with placebo, at week 24. Disappointingly, researchers found that acute medication frequency was not reduced in the overall treatment group, but they did note a significant reduction in the subgroup that was taking triptans. Moreover, a follow-up analysis by Aurora and colleagues involving 32 weeks of open-label treatment with onabotulinumtoxin A following the 24-week randomized study revealed significant reductions in acute headache days at 56 weeks.

Using anti-CGRPs without acute medication withdrawal

More recently, strong evidence is emerging about the value of using anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies without acute medication withdrawal. The findings involve 4 anti-CGRP medications.

Erenumab: A subgroup analysis of a randomized, double-blind, placebo-controlled parallel-group trial by Tepper and colleagues showed that erenumab reduced frequency of migraine at 3 months in participants with chronic migraine and medication overuse. Patients receiving either 70 or 140 mg of erenumab saw their migraine frequency reduced by an average of 6.6 days, versus 3.5 days in the placebo group. 

Additionally, a significantly greater number of patients in the treatment groups stopped overusing medication, and did so early, which led to improved patient-reported outcomes. Acute migraine-specific medication treatment days were reduced by an average of 5.4 days in the 70 mg group, 4.9 days in the 140 mg contingent, and 2.9 days in those who received placebo.

Overall, consistent improvement in measures of impact, disability and health-related quality of life were seen in individuals’ treatment with erenumab.

Galcanezumab: A post-hoc analysis of pooled data from the phase 3 EVOLVE-1 and EVOLVE-2 studies, as well as the phase 3 REGAIN trial found that in participants with medication overuse, 120 mg and 240 mg doses of galcanezumab cut the number of average migraine days and decreased medication overuse. Average migraine days were lowered in EVOLVE participants by 6.26 days in the 120 mg group, 5.77 days in the 240 mg contingent, and 2.71 in those who received placebo. In REGAIN, these numbers were 4.78, 4.51, and 2.25, respectively. Average monthly medication use rates in EVOLVE were 6.2%, 7.9%, and 15.9%, respectively; in REGAIN they were 24.3%, 23.1%, and 40.6%, respectively.

Notably, though the study demonstrated galcanezumab’s efficacy in those with and without medication overuse, improvement was more pronounced in patients with medication overuse.

Fremanezumab: In an analysis by Silberstein and colleagues, significantly more patients who received quarterly or monthly injections of fremanezumab reported no medication overuse during the 3-month study, versus placebo. Specifically, 61% of participants who received monthly injections of fremanezumab and 55% of those who took quarterly injections reported no medication overuse. Among those receiving placebo, only 46% reverted to no overuse. The effect was seen as early as week 4. Additionally, among patients with medication overuse at baseline, the number of days with acute medication use was significantly lower in the treatment groups versus placebo—1.8 days lower in the quarterly group and 2.8 days in the monthly contingent.

A subsequent post-hoc analysis presented at the 2019 American Headache Society (AHS) Annual Scientific Meeting showed that the benefits were sustained over time and the medication was effective in difficult cases. Continued treatment with either quarterly or monthly dosing resulted in a reduced number of headache days, acute medication overuse headache, and headache-related disability, compared with baseline measures. Notably, about 6 in every 10 individuals with medication overuse at baseline who received fremanezumab reverted to no acute medication overuse at 6 months. This effect was maintained through 1 year of treatment.

Eptinezumab: In PROMISE-2, a post-hoc analysis of the phase 3 trials evaluating quarterly IV infusions of eptinezumab 100 mg and 300 mg, Lipton and colleagues reported that participants with chronic migraine and medication overuse experienced greater reductions in monthly migraine days during weeks 1 through 12, versus placebo (100 mg, 7.7 days; 300 mg, 8.2 days; placebo, 5.6 days). Benefits, seen as early as the day after dosing, were generally maintained or improved over 24 weeks.

Acute care medication use was reduced by about 50% in the treatment group versus roughly 25% in the placebo contingent. Most encouraging was the finding that about one-third of individuals in the treatment cohort experienced 6 months without medication overuse and below the chronic migraine diagnostic threshold; only 10% of patients who received placebo resolved in this way. Consistent improvement across patient-reported outcomes was also observed in the treatment group versus placebo.

While the studies involving topiramate, onabotulinumtoxin A, and the anti-CGRP monoclonal antibodies suggest that preventive treatment alone may effectively treat acute medical overuse and medication overuse headache, it is the data behind the anti-CGRP treatments that seem to be most compelling and causing conventional thinking to be challenged. These medications appear to be able to convert individuals with chronic migraine and medication overuse, out of overuse and back to episodic migraine. Moreover, results show they may be able to reduce acute medication use in episodic migraine, which reduces the risk of the headache sufferer transforming to chronic migraine. It is worth considering this approach in patients’ overuse acute care medication, as well as those in whom discontinuation may otherwise prove difficult without concurrent preventive treatment.

The emerging role of gepants

Availability of the so-called “gepants”—small molecule CGRP receptor agonists—is shedding additional light on management of medication overuse headache and pointing to the future. Gepants—which include ubrogepant, rimegepant, and atogepant—have been shown in early data to have a preventive effect when used regularly. Thus, it is much less likely that their use will lead to excess use and medication overuse headache.

Preclinical data demonstrated that continued use of ubrogepant does not appear to produce early or latent trigeminal sensory sensitization. Meanwhile, rimegepant, when used every other day, and as needed for acute treatment of migraine in individuals suffering from moderate-to-high frequency episodic migraine, resulted in reductions in monthly migraine days. The preventive effects appear to be rapid and sustained. And in a phase 3 trial, atogepant demonstrated efficacy at doses of 10 mg, 30 mg, and 60 mg twice a day, compared with placebo over 12 weeks.

It is important to note that the link between the gepants and medication overuse and medication overuse headache have not yet been studied. Still, it is encouraging to see that migraine frequency improves and medication use days are reduced when gepants are taken preventively. Thus, gepants could emerge as a preferred approach for acute or preventive treatment in individuals who have or are at risk of developing medication overuse headache.