The turf war between two types of anesthesia providers is escalating: The American Society of Anesthesiologists (ASA) has filed a trademark complaint against the recently renamed American Association of Nurse Anesthesiology (AANA), alleging its use of the word “anesthesiology” is “deceptively misdescriptive.”

At issue: Who can be called an anesthesiologist?

In its complaint, filed in June 2024 with the US Trademark Trial and Appeal Board, the 54,000-member physician society seeks to deny the nurse group the registration of its trademark. If ASA wins, it could sue AANA in federal court.

AANA denied the physicians’ allegations in its recent response to the complaint.

The dispute between the two associations comes at a time when physicians are facing challenges from providers such as nurse practitioners and physician assistants who seek new titles and more autonomy in medical decision-making.
 

A Controversial Name Change

In 2021, the 61,000-member AANA changed its name from the American Association of Nurse Anesthetists, saying the change “clarifies” the role of its members.

The ASA declared it was “gravely concerned” by the name change, which “confuses patients and creates discord in the care setting, ultimately risking patient safety.

“ ’Anesthesiologist’ has always been used to differentiate physicians trained in the science and study of anesthesiology from nonphysicians, including nurse anesthetists,” the physicians’ group said in a news release.

Chicago Intellectual Property Attorney Laura M. Schaefer, who represents AANA, told this news organization that certified registered nurse anesthetists (CRNAs) — “also known as nurse anesthesiologists or nurse anesthetists — have a 150-year track record of administering safe, effective anesthesia to patients in need of care. Not only are CRNAs highly trained and capable, they also use the exact same techniques to provide anesthesia as other anesthesiology professionals.”

Ms. Schaefer declined to comment further, and ASA declined to comment at all, citing pending litigation.

The scope of practice of nurse anesthetists has long been disputed. In mid-September, California health officials clarified what nurse anesthetists can do on the job after complaints about lack of oversight, The Modesto Bee reported.

According to nursing education site NurseJournal.org, CRNAs and anesthesiologists “perform many of the same duties,” although CRNAs are in more demand. Also, the site says some states require CRNAs to be supervised by anesthesiologists.

“It is possible that scope of practice debates are increasing in prominence due to the increase in demand for healthcare services, coupled with workforce shortages in certain areas,” Alice Chen, PhD, MBA, vice dean for research at the USC Sol Price School of Public Policy in Los Angeles, told this news organization. “For example, during COVID, the federal government temporarily expanded scope of practice to help address healthcare needs.”

She added her group’s research has shown that despite the large stakes perceived by both sides of the debate, changes in practice behavior were actually quite small in states that allowed CRNAs to practice without supervision.

“In fact, we found only modest reduction in anesthesiologist billing for supervision, and we did not find an increase in the supply of anesthesia care,” she noted.

Trademark law specialists told this news organization that they couldn’t predict which way the board will rule. However, they noted potential weaknesses of the ASA’s case.

Rebecca Tushnet, JD, a professor at Harvard Law School, Cambridge, Massachusetts, explained that a trademark “can’t misrepresent those goods or services in a way that deceives consumers.” However, if insurers, doctors, and hospitals are considered the “consumers” — and not patients — “then confusion is probably less likely because they will have relevant expertise to distinguish among groups.”

Christine Farley, JD, LLM, JSD, professor at American University Washington College of Law, said attacking the AANA’s trademark as deceptive may be one of the ASA’s strongest arguments. The suggestion, she said, is that “nurse anesthesiologist” is an oxymoron, like “jumbo shrimp.”

On the other hand, she said it’s not clear that people will miss the word “nurse” in AANA’s name and say, “ ’Well, obviously these people are doctors.’ So that that’s an uphill battle.”

What happens now? The Trademark Trial and Appeal Board will decide whether AANA’s trademark application should be granted or denied, said Kayla Jimenez, JD, a San Diego trademark attorney and adjunct law professor at the University of San Diego. The entire process can take 2-3 years, she said.

The board “cannot award attorneys’ fees or force a party to stop using a trademark,” she said. “You would have to go file a lawsuit in federal court if that is your endgame.” Also, she said, the board’s ultimate decision can be appealed in federal court.

Eric Goldman, JD, MBA, associate dean for research and professor at Santa Clara University School of Law, Santa Clara, California, doesn’t expect the trademark case will spell the end of this dispute.

“ASA is signaling that it will challenge AANA’s use of the term in multiple battlegrounds,” he said. “I see this as a move by ASA to contest AANA in every potentially relevant venue, even if neither side can score a knockout blow in the Trademark Trial and Appeal Board.”

Dr. Chen, Ms. Farley, Ms. Jimenez, and Mr. Goldman had no disclosures. 
 

A version of this article appeared on Medscape.com.

The turf war between two types of anesthesia providers is escalating: The American Society of Anesthesiologists (ASA) has filed a trademark complaint against the recently renamed American Association of Nurse Anesthesiology (AANA), alleging its use of the word “anesthesiology” is “deceptively misdescriptive.”

At issue: Who can be called an anesthesiologist?

In its complaint, filed in June 2024 with the US Trademark Trial and Appeal Board, the 54,000-member physician society seeks to deny the nurse group the registration of its trademark. If ASA wins, it could sue AANA in federal court.

AANA denied the physicians’ allegations in its recent response to the complaint.

The dispute between the two associations comes at a time when physicians are facing challenges from providers such as nurse practitioners and physician assistants who seek new titles and more autonomy in medical decision-making.
 

A Controversial Name Change

In 2021, the 61,000-member AANA changed its name from the American Association of Nurse Anesthetists, saying the change “clarifies” the role of its members.

The ASA declared it was “gravely concerned” by the name change, which “confuses patients and creates discord in the care setting, ultimately risking patient safety.

“ ’Anesthesiologist’ has always been used to differentiate physicians trained in the science and study of anesthesiology from nonphysicians, including nurse anesthetists,” the physicians’ group said in a news release.

Chicago Intellectual Property Attorney Laura M. Schaefer, who represents AANA, told this news organization that certified registered nurse anesthetists (CRNAs) — “also known as nurse anesthesiologists or nurse anesthetists — have a 150-year track record of administering safe, effective anesthesia to patients in need of care. Not only are CRNAs highly trained and capable, they also use the exact same techniques to provide anesthesia as other anesthesiology professionals.”

Ms. Schaefer declined to comment further, and ASA declined to comment at all, citing pending litigation.

The scope of practice of nurse anesthetists has long been disputed. In mid-September, California health officials clarified what nurse anesthetists can do on the job after complaints about lack of oversight, The Modesto Bee reported.

According to nursing education site NurseJournal.org, CRNAs and anesthesiologists “perform many of the same duties,” although CRNAs are in more demand. Also, the site says some states require CRNAs to be supervised by anesthesiologists.

“It is possible that scope of practice debates are increasing in prominence due to the increase in demand for healthcare services, coupled with workforce shortages in certain areas,” Alice Chen, PhD, MBA, vice dean for research at the USC Sol Price School of Public Policy in Los Angeles, told this news organization. “For example, during COVID, the federal government temporarily expanded scope of practice to help address healthcare needs.”

She added her group’s research has shown that despite the large stakes perceived by both sides of the debate, changes in practice behavior were actually quite small in states that allowed CRNAs to practice without supervision.

“In fact, we found only modest reduction in anesthesiologist billing for supervision, and we did not find an increase in the supply of anesthesia care,” she noted.

Trademark law specialists told this news organization that they couldn’t predict which way the board will rule. However, they noted potential weaknesses of the ASA’s case.

Rebecca Tushnet, JD, a professor at Harvard Law School, Cambridge, Massachusetts, explained that a trademark “can’t misrepresent those goods or services in a way that deceives consumers.” However, if insurers, doctors, and hospitals are considered the “consumers” — and not patients — “then confusion is probably less likely because they will have relevant expertise to distinguish among groups.”

Christine Farley, JD, LLM, JSD, professor at American University Washington College of Law, said attacking the AANA’s trademark as deceptive may be one of the ASA’s strongest arguments. The suggestion, she said, is that “nurse anesthesiologist” is an oxymoron, like “jumbo shrimp.”

On the other hand, she said it’s not clear that people will miss the word “nurse” in AANA’s name and say, “ ’Well, obviously these people are doctors.’ So that that’s an uphill battle.”

What happens now? The Trademark Trial and Appeal Board will decide whether AANA’s trademark application should be granted or denied, said Kayla Jimenez, JD, a San Diego trademark attorney and adjunct law professor at the University of San Diego. The entire process can take 2-3 years, she said.

The board “cannot award attorneys’ fees or force a party to stop using a trademark,” she said. “You would have to go file a lawsuit in federal court if that is your endgame.” Also, she said, the board’s ultimate decision can be appealed in federal court.

Eric Goldman, JD, MBA, associate dean for research and professor at Santa Clara University School of Law, Santa Clara, California, doesn’t expect the trademark case will spell the end of this dispute.

“ASA is signaling that it will challenge AANA’s use of the term in multiple battlegrounds,” he said. “I see this as a move by ASA to contest AANA in every potentially relevant venue, even if neither side can score a knockout blow in the Trademark Trial and Appeal Board.”

Dr. Chen, Ms. Farley, Ms. Jimenez, and Mr. Goldman had no disclosures. 
 

A version of this article appeared on Medscape.com.

The turf war between two types of anesthesia providers is escalating: The American Society of Anesthesiologists (ASA) has filed a trademark complaint against the recently renamed American Association of Nurse Anesthesiology (AANA), alleging its use of the word “anesthesiology” is “deceptively misdescriptive.”

At issue: Who can be called an anesthesiologist?

In its complaint, filed in June 2024 with the US Trademark Trial and Appeal Board, the 54,000-member physician society seeks to deny the nurse group the registration of its trademark. If ASA wins, it could sue AANA in federal court.

AANA denied the physicians’ allegations in its recent response to the complaint.

The dispute between the two associations comes at a time when physicians are facing challenges from providers such as nurse practitioners and physician assistants who seek new titles and more autonomy in medical decision-making.
 

A Controversial Name Change

In 2021, the 61,000-member AANA changed its name from the American Association of Nurse Anesthetists, saying the change “clarifies” the role of its members.

The ASA declared it was “gravely concerned” by the name change, which “confuses patients and creates discord in the care setting, ultimately risking patient safety.

“ ’Anesthesiologist’ has always been used to differentiate physicians trained in the science and study of anesthesiology from nonphysicians, including nurse anesthetists,” the physicians’ group said in a news release.

Chicago Intellectual Property Attorney Laura M. Schaefer, who represents AANA, told this news organization that certified registered nurse anesthetists (CRNAs) — “also known as nurse anesthesiologists or nurse anesthetists — have a 150-year track record of administering safe, effective anesthesia to patients in need of care. Not only are CRNAs highly trained and capable, they also use the exact same techniques to provide anesthesia as other anesthesiology professionals.”

Ms. Schaefer declined to comment further, and ASA declined to comment at all, citing pending litigation.

The scope of practice of nurse anesthetists has long been disputed. In mid-September, California health officials clarified what nurse anesthetists can do on the job after complaints about lack of oversight, The Modesto Bee reported.

According to nursing education site NurseJournal.org, CRNAs and anesthesiologists “perform many of the same duties,” although CRNAs are in more demand. Also, the site says some states require CRNAs to be supervised by anesthesiologists.

“It is possible that scope of practice debates are increasing in prominence due to the increase in demand for healthcare services, coupled with workforce shortages in certain areas,” Alice Chen, PhD, MBA, vice dean for research at the USC Sol Price School of Public Policy in Los Angeles, told this news organization. “For example, during COVID, the federal government temporarily expanded scope of practice to help address healthcare needs.”

She added her group’s research has shown that despite the large stakes perceived by both sides of the debate, changes in practice behavior were actually quite small in states that allowed CRNAs to practice without supervision.

“In fact, we found only modest reduction in anesthesiologist billing for supervision, and we did not find an increase in the supply of anesthesia care,” she noted.

Trademark law specialists told this news organization that they couldn’t predict which way the board will rule. However, they noted potential weaknesses of the ASA’s case.

Rebecca Tushnet, JD, a professor at Harvard Law School, Cambridge, Massachusetts, explained that a trademark “can’t misrepresent those goods or services in a way that deceives consumers.” However, if insurers, doctors, and hospitals are considered the “consumers” — and not patients — “then confusion is probably less likely because they will have relevant expertise to distinguish among groups.”

Christine Farley, JD, LLM, JSD, professor at American University Washington College of Law, said attacking the AANA’s trademark as deceptive may be one of the ASA’s strongest arguments. The suggestion, she said, is that “nurse anesthesiologist” is an oxymoron, like “jumbo shrimp.”

On the other hand, she said it’s not clear that people will miss the word “nurse” in AANA’s name and say, “ ’Well, obviously these people are doctors.’ So that that’s an uphill battle.”

What happens now? The Trademark Trial and Appeal Board will decide whether AANA’s trademark application should be granted or denied, said Kayla Jimenez, JD, a San Diego trademark attorney and adjunct law professor at the University of San Diego. The entire process can take 2-3 years, she said.

The board “cannot award attorneys’ fees or force a party to stop using a trademark,” she said. “You would have to go file a lawsuit in federal court if that is your endgame.” Also, she said, the board’s ultimate decision can be appealed in federal court.

Eric Goldman, JD, MBA, associate dean for research and professor at Santa Clara University School of Law, Santa Clara, California, doesn’t expect the trademark case will spell the end of this dispute.

“ASA is signaling that it will challenge AANA’s use of the term in multiple battlegrounds,” he said. “I see this as a move by ASA to contest AANA in every potentially relevant venue, even if neither side can score a knockout blow in the Trademark Trial and Appeal Board.”

Dr. Chen, Ms. Farley, Ms. Jimenez, and Mr. Goldman had no disclosures. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Medicare Advantage plans had lower adjusted total resource use than traditional Medicare for patients with cancer undergoing chemotherapy, with no difference in 18-month survival between the two groups.

METHODOLOGY:

• Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
• Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
• The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
• Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
• Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.

TAKEAWAY:

• Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
• The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
• Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
• There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.

IN PRACTICE:

“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.

SOURCE:

The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.

LIMITATIONS:

The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.

DISCLOSURES:

Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Medicare Advantage plans had lower adjusted total resource use than traditional Medicare for patients with cancer undergoing chemotherapy, with no difference in 18-month survival between the two groups.

METHODOLOGY:

• Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
• Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
• The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
• Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
• Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.

TAKEAWAY:

• Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
• The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
• Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
• There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.

IN PRACTICE:

“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.

SOURCE:

The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.

LIMITATIONS:

The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.

DISCLOSURES:

Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Medicare Advantage plans had lower adjusted total resource use than traditional Medicare for patients with cancer undergoing chemotherapy, with no difference in 18-month survival between the two groups.

METHODOLOGY:

• Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
• Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
• The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
• Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
• Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.

TAKEAWAY:

• Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
• The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
• Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
• There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.

IN PRACTICE:

“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.

SOURCE:

The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.

LIMITATIONS:

The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.

DISCLOSURES:

Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Our dermatology department is composed of 25 doctors spread across 4 offices. It can be difficult to sustain cohesion so we have a few rituals to help hold us together. One is the morning huddle. This is a stand-up meeting lasting 3-5 minutes at 8:42 a.m. (just before the 8:45 a.m. patients). Led by our staff, huddle is a quick review of the priorities, issues, and celebrations across our department. While enthusiastically celebrating a staff member’s promotion one morning, a patient swung open the exam door and shouted, “What’s going on out here?! I’m sitting here waiting!” before slamming the door closed again. “Well, that was unnecessary,” our morning lead interjected as she went to reprimand him.

His behavior was easily recognizable to any doctor with children. It was an emotional outburst we call a tantrum. Although a graphic of tantrums by age would show a steep curve that drops precipitously after 4-years-old (please God, I hope), it persists throughout life. Even adults have tantrums. After? When I broke my pinky toe saving the family from flaming tornadoes a few weeks ago (I ran into the sofa), I flung the ice bag across the room in frustration. “You’ve a right to be mad,” my wife said returning the ice to where I was elevating my foot. She was spot on, it is understandable that I would be angry. It will be weeks before I can run again. And also my toe was broken. Both things were true.

Dr. Benabio

“Two things are true” is a technique for managing tantrums in toddlers. I first learned of it from Dr. Becky Kennedy, a clinical psychologist specializing in family therapy. She has a popular podcast called “Good Inside” based on her book of the same name. Her approach is to use positive psychology with an emphasis on connecting with children to not only shape behavior, but also to help them learn to manage their emotions. I read her book to level up dad skills and realized many of her principles are applicable to various types of relationships. Instead of viewing behaviors as an end, she instead recommends using them as an opportunity to probe for understanding. When someone exhibits poor behavior rather than assume they are being a jerk, try to find the most generous interpretation of what just happened. Assume they are doing the best they can. When my 4-year-old obstinately refused to go to bed despite the usual colored night lights and bedtime rituals, it seemed she was being a typical tantrum-y toddler. The more I insisted — lights-out! the more she resisted. It wasn’t until I asked why that I learned she was worried that the trash truck was going to come overnight. What seemed like just a behavioral problem, time for bed, was actually an opportunity for her to be seen and for us to connect.

I was finishing up with a patient last week when my medical assistant interrupted to advise my next patient was leaving. I walked out to see her storm into the corridor heading for the exit. “I am sorry, you must be quite frustrated having to wait for me.” “Yes, you don’t respect my time,” she said loudly enough for everyone pretending to not notice. I coaxed her back into the room and sat down. After apologizing for her wait and explaining it was because an urgent patient had been added to my schedule, she calmed down and allowed me to continue. At her previous visit, I had biopsied a firm dermal papule on her upper abdomen that turned out to be metastatic breast cancer. She was treated years ago and believed she was in complete remission. Now she was alone, terrified, and wanted her full appointment with me. Because I was running late, she assumed I wouldn’t have the time for her. It was an opportunity for me to connect with her and help her feel safe. I would have missed that opportunity if I had labeled her as just another angry “Karen” brassly asserting herself.

Dr. Kennedy talks a lot in her book about taking the “Most generous interpretation” of whatever behavioral issue arises. Take the time to validate what they are feeling and empathize as best as we can. Acknowledge that it’s normal to be angry and also these are the truths we have to work with. Two truths commonly appear in these emotional episodes. One, the immutable facts, for example, insurance doesn’t cover that drug, and two, your right to be frustrated by that. Above all, remember you, the doctor, are good inside as is your discourteous patient, disaffected staff member or sometimes mendacious teenager. “All good decisions start with feeling secure and nothing feels more secure than being recognized for the good people we are,” says Dr. Kennedy. True I believe even if we sometimes slam the door.

Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.

Our dermatology department is composed of 25 doctors spread across 4 offices. It can be difficult to sustain cohesion so we have a few rituals to help hold us together. One is the morning huddle. This is a stand-up meeting lasting 3-5 minutes at 8:42 a.m. (just before the 8:45 a.m. patients). Led by our staff, huddle is a quick review of the priorities, issues, and celebrations across our department. While enthusiastically celebrating a staff member’s promotion one morning, a patient swung open the exam door and shouted, “What’s going on out here?! I’m sitting here waiting!” before slamming the door closed again. “Well, that was unnecessary,” our morning lead interjected as she went to reprimand him.

His behavior was easily recognizable to any doctor with children. It was an emotional outburst we call a tantrum. Although a graphic of tantrums by age would show a steep curve that drops precipitously after 4-years-old (please God, I hope), it persists throughout life. Even adults have tantrums. After? When I broke my pinky toe saving the family from flaming tornadoes a few weeks ago (I ran into the sofa), I flung the ice bag across the room in frustration. “You’ve a right to be mad,” my wife said returning the ice to where I was elevating my foot. She was spot on, it is understandable that I would be angry. It will be weeks before I can run again. And also my toe was broken. Both things were true.

Dr. Benabio

“Two things are true” is a technique for managing tantrums in toddlers. I first learned of it from Dr. Becky Kennedy, a clinical psychologist specializing in family therapy. She has a popular podcast called “Good Inside” based on her book of the same name. Her approach is to use positive psychology with an emphasis on connecting with children to not only shape behavior, but also to help them learn to manage their emotions. I read her book to level up dad skills and realized many of her principles are applicable to various types of relationships. Instead of viewing behaviors as an end, she instead recommends using them as an opportunity to probe for understanding. When someone exhibits poor behavior rather than assume they are being a jerk, try to find the most generous interpretation of what just happened. Assume they are doing the best they can. When my 4-year-old obstinately refused to go to bed despite the usual colored night lights and bedtime rituals, it seemed she was being a typical tantrum-y toddler. The more I insisted — lights-out! the more she resisted. It wasn’t until I asked why that I learned she was worried that the trash truck was going to come overnight. What seemed like just a behavioral problem, time for bed, was actually an opportunity for her to be seen and for us to connect.

I was finishing up with a patient last week when my medical assistant interrupted to advise my next patient was leaving. I walked out to see her storm into the corridor heading for the exit. “I am sorry, you must be quite frustrated having to wait for me.” “Yes, you don’t respect my time,” she said loudly enough for everyone pretending to not notice. I coaxed her back into the room and sat down. After apologizing for her wait and explaining it was because an urgent patient had been added to my schedule, she calmed down and allowed me to continue. At her previous visit, I had biopsied a firm dermal papule on her upper abdomen that turned out to be metastatic breast cancer. She was treated years ago and believed she was in complete remission. Now she was alone, terrified, and wanted her full appointment with me. Because I was running late, she assumed I wouldn’t have the time for her. It was an opportunity for me to connect with her and help her feel safe. I would have missed that opportunity if I had labeled her as just another angry “Karen” brassly asserting herself.

Dr. Kennedy talks a lot in her book about taking the “Most generous interpretation” of whatever behavioral issue arises. Take the time to validate what they are feeling and empathize as best as we can. Acknowledge that it’s normal to be angry and also these are the truths we have to work with. Two truths commonly appear in these emotional episodes. One, the immutable facts, for example, insurance doesn’t cover that drug, and two, your right to be frustrated by that. Above all, remember you, the doctor, are good inside as is your discourteous patient, disaffected staff member or sometimes mendacious teenager. “All good decisions start with feeling secure and nothing feels more secure than being recognized for the good people we are,” says Dr. Kennedy. True I believe even if we sometimes slam the door.

Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.

Our dermatology department is composed of 25 doctors spread across 4 offices. It can be difficult to sustain cohesion so we have a few rituals to help hold us together. One is the morning huddle. This is a stand-up meeting lasting 3-5 minutes at 8:42 a.m. (just before the 8:45 a.m. patients). Led by our staff, huddle is a quick review of the priorities, issues, and celebrations across our department. While enthusiastically celebrating a staff member’s promotion one morning, a patient swung open the exam door and shouted, “What’s going on out here?! I’m sitting here waiting!” before slamming the door closed again. “Well, that was unnecessary,” our morning lead interjected as she went to reprimand him.

His behavior was easily recognizable to any doctor with children. It was an emotional outburst we call a tantrum. Although a graphic of tantrums by age would show a steep curve that drops precipitously after 4-years-old (please God, I hope), it persists throughout life. Even adults have tantrums. After? When I broke my pinky toe saving the family from flaming tornadoes a few weeks ago (I ran into the sofa), I flung the ice bag across the room in frustration. “You’ve a right to be mad,” my wife said returning the ice to where I was elevating my foot. She was spot on, it is understandable that I would be angry. It will be weeks before I can run again. And also my toe was broken. Both things were true.

Dr. Benabio

“Two things are true” is a technique for managing tantrums in toddlers. I first learned of it from Dr. Becky Kennedy, a clinical psychologist specializing in family therapy. She has a popular podcast called “Good Inside” based on her book of the same name. Her approach is to use positive psychology with an emphasis on connecting with children to not only shape behavior, but also to help them learn to manage their emotions. I read her book to level up dad skills and realized many of her principles are applicable to various types of relationships. Instead of viewing behaviors as an end, she instead recommends using them as an opportunity to probe for understanding. When someone exhibits poor behavior rather than assume they are being a jerk, try to find the most generous interpretation of what just happened. Assume they are doing the best they can. When my 4-year-old obstinately refused to go to bed despite the usual colored night lights and bedtime rituals, it seemed she was being a typical tantrum-y toddler. The more I insisted — lights-out! the more she resisted. It wasn’t until I asked why that I learned she was worried that the trash truck was going to come overnight. What seemed like just a behavioral problem, time for bed, was actually an opportunity for her to be seen and for us to connect.

I was finishing up with a patient last week when my medical assistant interrupted to advise my next patient was leaving. I walked out to see her storm into the corridor heading for the exit. “I am sorry, you must be quite frustrated having to wait for me.” “Yes, you don’t respect my time,” she said loudly enough for everyone pretending to not notice. I coaxed her back into the room and sat down. After apologizing for her wait and explaining it was because an urgent patient had been added to my schedule, she calmed down and allowed me to continue. At her previous visit, I had biopsied a firm dermal papule on her upper abdomen that turned out to be metastatic breast cancer. She was treated years ago and believed she was in complete remission. Now she was alone, terrified, and wanted her full appointment with me. Because I was running late, she assumed I wouldn’t have the time for her. It was an opportunity for me to connect with her and help her feel safe. I would have missed that opportunity if I had labeled her as just another angry “Karen” brassly asserting herself.

Dr. Kennedy talks a lot in her book about taking the “Most generous interpretation” of whatever behavioral issue arises. Take the time to validate what they are feeling and empathize as best as we can. Acknowledge that it’s normal to be angry and also these are the truths we have to work with. Two truths commonly appear in these emotional episodes. One, the immutable facts, for example, insurance doesn’t cover that drug, and two, your right to be frustrated by that. Above all, remember you, the doctor, are good inside as is your discourteous patient, disaffected staff member or sometimes mendacious teenager. “All good decisions start with feeling secure and nothing feels more secure than being recognized for the good people we are,” says Dr. Kennedy. True I believe even if we sometimes slam the door.

Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.

TOPLINE:

Treatment-resistant major depression (TRD) is associated with a 17% higher risk for all-cause mortality than non-TRD major depressive disorder (MDD), a new study shows. The increased mortality risk was driven largely by suicide and accidental overdose, which were nearly twice as high among people whose depression didn’t improve after two treatments. 

METHODOLOGY:

• Data on 176,942 individuals diagnosed with MDD and treated with an antidepressant (median age at diagnosis, 40 years; 63% women) were obtained from Finnish nationwide registers.
• About 11% of the participants had TRD, defined as having more than two adequate treatment trials of at least 28 days, each within 2 years from the index antidepressant prescription.
• The outcomes were all-cause and cause-specific mortality, with demographic characteristics, psychiatric comorbidities, and treatment history included as covariates.
• The median follow-up period was 8.9 years.

TAKEAWAY:

• Median time to TRD was 8 months, and 959 and 7662 deaths were observed in the TRD and non-TRD groups, respectively.
• All-cause mortality was 17% higher among patients with TRD than among those with non-TRD (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.09-1.25) because of higher mortality to external causes.
• Mortalities because of suicides (aHR, 1.90; 95% CI, 1.64-2.20) and accidental poisonings (aHR, 1.81; 95% CI, 1.48-2.22) were almost double in the TRD group, compared with the non-TRD group.
• No significant difference in mortality due to natural causes was observed between the TRD and non-TRD groups.

IN PRACTICE:

“The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher-intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression,” the study authors wrote.

SOURCE:

The study was led by Tapio T. Gustafsson, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online on September 11, 2024, in The Journal of Affective Disorders.

LIMITATIONS:

The definition of TRD lacked consensus. The study used routine data to define TRD, which may not have captured all relevant clinical nuances. Additionally, the reasons for medication changes were unavailable.

DISCLOSURES:

This study was funded by Johnson & Johnson Innovative Medicine and Niuvanniemi Hospital, with support from the Finnish Ministry of Social Affairs and Health. Several authors disclosed financial relationships with various pharmaceutical companies, and two are employees of Johnson & Johnson Innovative Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Treatment-resistant major depression (TRD) is associated with a 17% higher risk for all-cause mortality than non-TRD major depressive disorder (MDD), a new study shows. The increased mortality risk was driven largely by suicide and accidental overdose, which were nearly twice as high among people whose depression didn’t improve after two treatments. 

METHODOLOGY:

• Data on 176,942 individuals diagnosed with MDD and treated with an antidepressant (median age at diagnosis, 40 years; 63% women) were obtained from Finnish nationwide registers.
• About 11% of the participants had TRD, defined as having more than two adequate treatment trials of at least 28 days, each within 2 years from the index antidepressant prescription.
• The outcomes were all-cause and cause-specific mortality, with demographic characteristics, psychiatric comorbidities, and treatment history included as covariates.
• The median follow-up period was 8.9 years.

TAKEAWAY:

• Median time to TRD was 8 months, and 959 and 7662 deaths were observed in the TRD and non-TRD groups, respectively.
• All-cause mortality was 17% higher among patients with TRD than among those with non-TRD (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.09-1.25) because of higher mortality to external causes.
• Mortalities because of suicides (aHR, 1.90; 95% CI, 1.64-2.20) and accidental poisonings (aHR, 1.81; 95% CI, 1.48-2.22) were almost double in the TRD group, compared with the non-TRD group.
• No significant difference in mortality due to natural causes was observed between the TRD and non-TRD groups.

IN PRACTICE:

“The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher-intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression,” the study authors wrote.

SOURCE:

The study was led by Tapio T. Gustafsson, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online on September 11, 2024, in The Journal of Affective Disorders.

LIMITATIONS:

The definition of TRD lacked consensus. The study used routine data to define TRD, which may not have captured all relevant clinical nuances. Additionally, the reasons for medication changes were unavailable.

DISCLOSURES:

This study was funded by Johnson & Johnson Innovative Medicine and Niuvanniemi Hospital, with support from the Finnish Ministry of Social Affairs and Health. Several authors disclosed financial relationships with various pharmaceutical companies, and two are employees of Johnson & Johnson Innovative Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Treatment-resistant major depression (TRD) is associated with a 17% higher risk for all-cause mortality than non-TRD major depressive disorder (MDD), a new study shows. The increased mortality risk was driven largely by suicide and accidental overdose, which were nearly twice as high among people whose depression didn’t improve after two treatments. 

METHODOLOGY:

• Data on 176,942 individuals diagnosed with MDD and treated with an antidepressant (median age at diagnosis, 40 years; 63% women) were obtained from Finnish nationwide registers.
• About 11% of the participants had TRD, defined as having more than two adequate treatment trials of at least 28 days, each within 2 years from the index antidepressant prescription.
• The outcomes were all-cause and cause-specific mortality, with demographic characteristics, psychiatric comorbidities, and treatment history included as covariates.
• The median follow-up period was 8.9 years.

TAKEAWAY:

• Median time to TRD was 8 months, and 959 and 7662 deaths were observed in the TRD and non-TRD groups, respectively.
• All-cause mortality was 17% higher among patients with TRD than among those with non-TRD (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.09-1.25) because of higher mortality to external causes.
• Mortalities because of suicides (aHR, 1.90; 95% CI, 1.64-2.20) and accidental poisonings (aHR, 1.81; 95% CI, 1.48-2.22) were almost double in the TRD group, compared with the non-TRD group.
• No significant difference in mortality due to natural causes was observed between the TRD and non-TRD groups.

IN PRACTICE:

“The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher-intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression,” the study authors wrote.

SOURCE:

The study was led by Tapio T. Gustafsson, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online on September 11, 2024, in The Journal of Affective Disorders.

LIMITATIONS:

The definition of TRD lacked consensus. The study used routine data to define TRD, which may not have captured all relevant clinical nuances. Additionally, the reasons for medication changes were unavailable.

DISCLOSURES:

This study was funded by Johnson & Johnson Innovative Medicine and Niuvanniemi Hospital, with support from the Finnish Ministry of Social Affairs and Health. Several authors disclosed financial relationships with various pharmaceutical companies, and two are employees of Johnson & Johnson Innovative Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Electronic health record (EHR)–derived family history identified 29,913 patients with familial risk for hereditary breast and ovarian cancer, but 82% had no evidence of genetic testing. Seven-question family history screening (FHS7)–positive status was associated with a threefold increase in BRCA1/2 positivity and a 44% increase in cancer risk among women.

METHODOLOGY:

• A cross-sectional and retrospective cohort analysis used EHR data from Renown Health in northern Nevada. The study period spanned from January 1, 2018, to February 1, 2024, with data on demographic variables, healthcare utilization, and cancer diagnoses.
• The study aimed to use the FHS7 to identify patients meeting family history criteria for genetic testing (familial risk for hereditary breast and ovarian cancer) in their EHRs; patients meeting the FHS7 criteria were deemed to be FHS7-positive.
• A total of 835,727 patients aged 18-79 years were included, with genotype data available for 38,003 participants from the Healthy Nevada Project, which notified 330 individuals with BRCA1/2 variants of their genetic risk.
• The primary outcomes were the presence of pathogenic or likely pathogenic variants in specific genes and the diagnosis of cancer.

TAKEAWAY:

• FHS7-positive status was associated with a 3.34-fold increase in BRCA1/2 positivity among female participants and a 3.35-fold increase among male participants (95% CI, 2.48-4.47 and 1.93-5.56, respectively).
• Female FHS7-positive participants had a 1.62-fold increase in CHEK2 positivity and a 2.84-fold increase in PALB2 positivity (95% CI, 1.05-2.43 and 1.23-6.16, respectively).
• Age-adjusted cancer incidence rates were higher for FHS7-positive patients, with 367.2 cases per 100,000 per year for women and 309.9 cases per 100,000 per year for men.
• The number needed to test to detect one BRCA1/2-positive patient decreased from 128 to 53 for women and from 119 to 42 for men when prescreening with FHS7.

IN PRACTICE:

“EHR-derived FHS7 identified thousands of patients with familial risk for breast cancer, indicating a substantial gap in genetic testing,” the study authors wrote. “Survey results suggest that most patients who are FHS7-positive in their EHR truly meet family history criteria, but that EHR-derived FHS7 may miss many patients who would be FHS7-positive if approached with a direct questionnaire,” the author wrote.

SOURCE:

The study was led by Daniel Kiser, MS, University of Nevada, Reno School of Medicine. It was published online in JAMA Network Open.

LIMITATIONS: 

The study’s observational design may introduce self-selection biases, particularly among Healthy Nevada Project participants. The 21.8% response rate to the survey suggests potential self-selection among respondents. The tendency of less healthy patients to have more data available in their EHRs could influence the authors’ analysis of cancer incidence rates, despite adjustments for healthcare utilization levels.

DISCLOSURES:

Daniel Kiser and Joseph J. Grzymski, PhD, reported holding patents outside the submitted work. Dr. Grzymski also disclosed receiving grants from Gilead Sciences. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Electronic health record (EHR)–derived family history identified 29,913 patients with familial risk for hereditary breast and ovarian cancer, but 82% had no evidence of genetic testing. Seven-question family history screening (FHS7)–positive status was associated with a threefold increase in BRCA1/2 positivity and a 44% increase in cancer risk among women.

METHODOLOGY:

• A cross-sectional and retrospective cohort analysis used EHR data from Renown Health in northern Nevada. The study period spanned from January 1, 2018, to February 1, 2024, with data on demographic variables, healthcare utilization, and cancer diagnoses.
• The study aimed to use the FHS7 to identify patients meeting family history criteria for genetic testing (familial risk for hereditary breast and ovarian cancer) in their EHRs; patients meeting the FHS7 criteria were deemed to be FHS7-positive.
• A total of 835,727 patients aged 18-79 years were included, with genotype data available for 38,003 participants from the Healthy Nevada Project, which notified 330 individuals with BRCA1/2 variants of their genetic risk.
• The primary outcomes were the presence of pathogenic or likely pathogenic variants in specific genes and the diagnosis of cancer.

TAKEAWAY:

• FHS7-positive status was associated with a 3.34-fold increase in BRCA1/2 positivity among female participants and a 3.35-fold increase among male participants (95% CI, 2.48-4.47 and 1.93-5.56, respectively).
• Female FHS7-positive participants had a 1.62-fold increase in CHEK2 positivity and a 2.84-fold increase in PALB2 positivity (95% CI, 1.05-2.43 and 1.23-6.16, respectively).
• Age-adjusted cancer incidence rates were higher for FHS7-positive patients, with 367.2 cases per 100,000 per year for women and 309.9 cases per 100,000 per year for men.
• The number needed to test to detect one BRCA1/2-positive patient decreased from 128 to 53 for women and from 119 to 42 for men when prescreening with FHS7.

IN PRACTICE:

“EHR-derived FHS7 identified thousands of patients with familial risk for breast cancer, indicating a substantial gap in genetic testing,” the study authors wrote. “Survey results suggest that most patients who are FHS7-positive in their EHR truly meet family history criteria, but that EHR-derived FHS7 may miss many patients who would be FHS7-positive if approached with a direct questionnaire,” the author wrote.

SOURCE:

The study was led by Daniel Kiser, MS, University of Nevada, Reno School of Medicine. It was published online in JAMA Network Open.

LIMITATIONS: 

The study’s observational design may introduce self-selection biases, particularly among Healthy Nevada Project participants. The 21.8% response rate to the survey suggests potential self-selection among respondents. The tendency of less healthy patients to have more data available in their EHRs could influence the authors’ analysis of cancer incidence rates, despite adjustments for healthcare utilization levels.

DISCLOSURES:

Daniel Kiser and Joseph J. Grzymski, PhD, reported holding patents outside the submitted work. Dr. Grzymski also disclosed receiving grants from Gilead Sciences. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Electronic health record (EHR)–derived family history identified 29,913 patients with familial risk for hereditary breast and ovarian cancer, but 82% had no evidence of genetic testing. Seven-question family history screening (FHS7)–positive status was associated with a threefold increase in BRCA1/2 positivity and a 44% increase in cancer risk among women.

METHODOLOGY:

• A cross-sectional and retrospective cohort analysis used EHR data from Renown Health in northern Nevada. The study period spanned from January 1, 2018, to February 1, 2024, with data on demographic variables, healthcare utilization, and cancer diagnoses.
• The study aimed to use the FHS7 to identify patients meeting family history criteria for genetic testing (familial risk for hereditary breast and ovarian cancer) in their EHRs; patients meeting the FHS7 criteria were deemed to be FHS7-positive.
• A total of 835,727 patients aged 18-79 years were included, with genotype data available for 38,003 participants from the Healthy Nevada Project, which notified 330 individuals with BRCA1/2 variants of their genetic risk.
• The primary outcomes were the presence of pathogenic or likely pathogenic variants in specific genes and the diagnosis of cancer.

TAKEAWAY:

• FHS7-positive status was associated with a 3.34-fold increase in BRCA1/2 positivity among female participants and a 3.35-fold increase among male participants (95% CI, 2.48-4.47 and 1.93-5.56, respectively).
• Female FHS7-positive participants had a 1.62-fold increase in CHEK2 positivity and a 2.84-fold increase in PALB2 positivity (95% CI, 1.05-2.43 and 1.23-6.16, respectively).
• Age-adjusted cancer incidence rates were higher for FHS7-positive patients, with 367.2 cases per 100,000 per year for women and 309.9 cases per 100,000 per year for men.
• The number needed to test to detect one BRCA1/2-positive patient decreased from 128 to 53 for women and from 119 to 42 for men when prescreening with FHS7.

IN PRACTICE:

“EHR-derived FHS7 identified thousands of patients with familial risk for breast cancer, indicating a substantial gap in genetic testing,” the study authors wrote. “Survey results suggest that most patients who are FHS7-positive in their EHR truly meet family history criteria, but that EHR-derived FHS7 may miss many patients who would be FHS7-positive if approached with a direct questionnaire,” the author wrote.

SOURCE:

The study was led by Daniel Kiser, MS, University of Nevada, Reno School of Medicine. It was published online in JAMA Network Open.

LIMITATIONS: 

The study’s observational design may introduce self-selection biases, particularly among Healthy Nevada Project participants. The 21.8% response rate to the survey suggests potential self-selection among respondents. The tendency of less healthy patients to have more data available in their EHRs could influence the authors’ analysis of cancer incidence rates, despite adjustments for healthcare utilization levels.

DISCLOSURES:

Daniel Kiser and Joseph J. Grzymski, PhD, reported holding patents outside the submitted work. Dr. Grzymski also disclosed receiving grants from Gilead Sciences. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

During the month of September, Sexual Health Awareness Month, it may help to notice something: Men and their doctors have significantly more options to help with sexual function than do women and their clinicians. Moreover, the education of physicians regarding the examination and treatment of women for sexual dysfunction has been and remains, even now in 2024, much less thorough than for men. 

Not convinced? Let’s take a quick tour.
 

The New Sexual Revolution and the Growing Anger

Around the time of the release of the book and movie Fifty Shades of Grey, Newsweek put the cultural sensation on its cover.

I bought the magazine at the airport and, while waiting for my plane, showed the story to a woman sitting next to me. “What do you think — is this the new ‘sexual revolution’?” I asked her.

She glanced at the cover and answered as accurately as if she had written the article: “In the ’60s, it became okay for women to have sex; now, it’s okay for women to demand good sex.”

I would add to that: Women are demanding good sex, and they want to define for themselves what “good” means.

That social revolution rages, still.

You would think that the demand would bring a corresponding response in clinical medicine. You would be wrong. Although efforts in some sectors are heroic, overall, the results are lagging the forward movement of women wanting better sex.
 

The Lag in Sexual Education

To examine the progression of the education of physicians regarding the treatment of female sexual dysfunction (FSD), Codispoti and colleagues examined the curricula of seven medical schools in and around Chicago. They found the following: Only one institution identified all anatomic components of the clitoris — one! Four of the seven discussed the physiology of the female orgasm. Only three of the seven highlighted the prevalence and epidemiology of FSD or the treatments for FSD. Only one of the seven explained how to do a genitourinary physical exam specific to assessing FSD. 

When assessing obstetrics and gynecology clinical materials, sexual pleasure, arousal, and libido were not included anywhere in the curricula.

I have been teaching physicians about the therapies I developed (over 5000 clinicians in 50-plus countries over the past 14 years). During those sessions, I often stop the class and ask, “Who in here was taught how to retract the foreskin and examine the penis for phimosis?”

All hands will go up.

Then I will ask, “Who in here was taught in medical school how to retract the clitoral hood and examine the clitoris for phimosis?”

Not once has anyone raised a hand.
 

The Sex Remedies Gap

When I first published research offering support for using platelet-rich plasma to improve sexual function in women, women had not one drug approved by the US Food and Drug Administration (FDA) for the treatment of sexual dysfunction — none. Men had over 20. Today, men have a growing number of FDA-approved drugs for erectile dysfunction, including the “fils”; women have three. 

Women have access to only one FDA-approved medication that primarily affects the genitalia: prasterone. This drug is indicated only for the treatment of pain in postmenopausal women. It does not directly enhance desire or improve orgasms. Said another way, although the incidence of sexual dysfunction is higher in premenopausal women than in other groups, they do not have a single approved medication designed to improve the function of their genitalia. 

The other two of the three available drugs — flibanserin and bremelanotide — primarily affect the brain and could accurately be called psychoactive agents. They are available only for premenopausal women to improve desire. Flibanserin resulted in one extra sexual encounter per month on average, and patients are advised to avoid alcohol while using the drug. The other can make you vomit.

I do think all three of these treatments can be of great help to some women. I am not advising their disappearance. But in contrast to what is available to men, they are woefully inadequate.
 

Historical Perspective

In 1980, the medical establishment believed “most instances of acquired impotence are psychogenic.” Then, with the accidental discovery of the benefits of phosphodiesterase type 5 inhibitors, we realized that most cases of male sexual dysfunction involve the vasculature of the genitalia, not the neuroses of the brain. Yet, our two FDA-approved drugs for women with sexual dysfunction are designed to affect the brain. Women have nothing but off-label therapies to improve the function of the genitalia.

Despite the fact research supports the use of testosterone in women for both libido and orgasm, and despite the fact millions of women are treated with testosterone off-label for the benefit of sexual function, the only widely used FDA-approved class of drugs for women that affects testosterone — birth control pills, by blocking pituitary hormone production (the way they prevent pregnancy) — lowers the production of testosterone. 

One might wonder, considering our expanded understanding of the endocrinology of both men and women, at the irony of why it is acceptable to lower the testosterone level of an adolescent girl knowingly, as if her development did not require the hormone (such would never be acceptable in an adolescent male unless sexual transitioning were the goal); yet, we are fearful of giving testosterone to grown women who can no longer make it.
 

Premenopausal Women: An Orphan Population

The concept of “orphan populations” can partially explain the gap in available therapies between men and women.

Women of childbearing age are risky to study; so, with testosterone, for example, it is safer and cheaper for pharmaceutical companies to prove the benefits for men and ride the profits from the off-label use for women. I don’t mean to condemn the manufacturers of testosterone, only to point out the phenomenon of why up to 30% of the prescriptions written by a primary care physician are off-label; off-label use is common among cardiologists (46%); up to 90% of children in the hospital receive at least one off-label drug; and approval of drugs for premenopausal women is more expensive than approval of drugs for men. 
 

What Can Be Done?

The regrettable situation does not reflect evil intent on the part of regulators, educators, or physicians. But the gap between what women want and what medical education and the pharmaceutical-regulatory complex are providing is intolerably wide.

First, I would recommend a standard, required curriculum for the study of female sexual anatomy and function be established and widely adopted by medical schools. The reproductive system contains different components and a different purpose from the orgasm system, with modest overlap. Both systems should be taught in every medical school.

Second, physicians should be required to undergo a course in understanding their own sexuality. Research demonstrates doctors will avoid conversations about sex, and it seems to me this could be secondary to being uncomfortable with their own sexuality. After all, to talk with a patient about sex, you cannot be fearful of where the conversation may lead.

Third, the FDA might reconsider the requirements for the approval of drugs for FSD. Currently, to approve a drug for men, an objective finding — ie, an erection — can be sufficient. However, a higher bar, “satisfaction,” which is subjective, must be obtained with women.

Regenerative therapies have proved helpful but are not yet widely adopted; more grant money for the study of regenerative therapies would be a good start here. 

Finally, by the definition of FSD, a woman must be psychologically distressed. The idea of sex is not pleasure alone. Sexual function affects family relationships, emotional health, confidence, even sleep, as well as the emotional well-being of the children who live in the house. Saying women are wonderfully and mysteriously made may be poetic, but it is not an excuse for not learning more and closing the gaps.

Dr. Runels is medical director of the Cellular Medicine Association, Fairhope, Alabama. He reported conflicts of interest with the Cellular Medicine Association, Runels Research Institute, Institute for Lichen Sclerosus, and Vulvar Health. A version of this article first appeared on Medscape.com.

During the month of September, Sexual Health Awareness Month, it may help to notice something: Men and their doctors have significantly more options to help with sexual function than do women and their clinicians. Moreover, the education of physicians regarding the examination and treatment of women for sexual dysfunction has been and remains, even now in 2024, much less thorough than for men. 

Not convinced? Let’s take a quick tour.
 

The New Sexual Revolution and the Growing Anger

Around the time of the release of the book and movie Fifty Shades of Grey, Newsweek put the cultural sensation on its cover.

I bought the magazine at the airport and, while waiting for my plane, showed the story to a woman sitting next to me. “What do you think — is this the new ‘sexual revolution’?” I asked her.

She glanced at the cover and answered as accurately as if she had written the article: “In the ’60s, it became okay for women to have sex; now, it’s okay for women to demand good sex.”

I would add to that: Women are demanding good sex, and they want to define for themselves what “good” means.

That social revolution rages, still.

You would think that the demand would bring a corresponding response in clinical medicine. You would be wrong. Although efforts in some sectors are heroic, overall, the results are lagging the forward movement of women wanting better sex.
 

The Lag in Sexual Education

To examine the progression of the education of physicians regarding the treatment of female sexual dysfunction (FSD), Codispoti and colleagues examined the curricula of seven medical schools in and around Chicago. They found the following: Only one institution identified all anatomic components of the clitoris — one! Four of the seven discussed the physiology of the female orgasm. Only three of the seven highlighted the prevalence and epidemiology of FSD or the treatments for FSD. Only one of the seven explained how to do a genitourinary physical exam specific to assessing FSD. 

When assessing obstetrics and gynecology clinical materials, sexual pleasure, arousal, and libido were not included anywhere in the curricula.

I have been teaching physicians about the therapies I developed (over 5000 clinicians in 50-plus countries over the past 14 years). During those sessions, I often stop the class and ask, “Who in here was taught how to retract the foreskin and examine the penis for phimosis?”

All hands will go up.

Then I will ask, “Who in here was taught in medical school how to retract the clitoral hood and examine the clitoris for phimosis?”

Not once has anyone raised a hand.
 

The Sex Remedies Gap

When I first published research offering support for using platelet-rich plasma to improve sexual function in women, women had not one drug approved by the US Food and Drug Administration (FDA) for the treatment of sexual dysfunction — none. Men had over 20. Today, men have a growing number of FDA-approved drugs for erectile dysfunction, including the “fils”; women have three. 

Women have access to only one FDA-approved medication that primarily affects the genitalia: prasterone. This drug is indicated only for the treatment of pain in postmenopausal women. It does not directly enhance desire or improve orgasms. Said another way, although the incidence of sexual dysfunction is higher in premenopausal women than in other groups, they do not have a single approved medication designed to improve the function of their genitalia. 

The other two of the three available drugs — flibanserin and bremelanotide — primarily affect the brain and could accurately be called psychoactive agents. They are available only for premenopausal women to improve desire. Flibanserin resulted in one extra sexual encounter per month on average, and patients are advised to avoid alcohol while using the drug. The other can make you vomit.

I do think all three of these treatments can be of great help to some women. I am not advising their disappearance. But in contrast to what is available to men, they are woefully inadequate.
 

Historical Perspective

In 1980, the medical establishment believed “most instances of acquired impotence are psychogenic.” Then, with the accidental discovery of the benefits of phosphodiesterase type 5 inhibitors, we realized that most cases of male sexual dysfunction involve the vasculature of the genitalia, not the neuroses of the brain. Yet, our two FDA-approved drugs for women with sexual dysfunction are designed to affect the brain. Women have nothing but off-label therapies to improve the function of the genitalia.

Despite the fact research supports the use of testosterone in women for both libido and orgasm, and despite the fact millions of women are treated with testosterone off-label for the benefit of sexual function, the only widely used FDA-approved class of drugs for women that affects testosterone — birth control pills, by blocking pituitary hormone production (the way they prevent pregnancy) — lowers the production of testosterone. 

One might wonder, considering our expanded understanding of the endocrinology of both men and women, at the irony of why it is acceptable to lower the testosterone level of an adolescent girl knowingly, as if her development did not require the hormone (such would never be acceptable in an adolescent male unless sexual transitioning were the goal); yet, we are fearful of giving testosterone to grown women who can no longer make it.
 

Premenopausal Women: An Orphan Population

The concept of “orphan populations” can partially explain the gap in available therapies between men and women.

Women of childbearing age are risky to study; so, with testosterone, for example, it is safer and cheaper for pharmaceutical companies to prove the benefits for men and ride the profits from the off-label use for women. I don’t mean to condemn the manufacturers of testosterone, only to point out the phenomenon of why up to 30% of the prescriptions written by a primary care physician are off-label; off-label use is common among cardiologists (46%); up to 90% of children in the hospital receive at least one off-label drug; and approval of drugs for premenopausal women is more expensive than approval of drugs for men. 
 

What Can Be Done?

The regrettable situation does not reflect evil intent on the part of regulators, educators, or physicians. But the gap between what women want and what medical education and the pharmaceutical-regulatory complex are providing is intolerably wide.

First, I would recommend a standard, required curriculum for the study of female sexual anatomy and function be established and widely adopted by medical schools. The reproductive system contains different components and a different purpose from the orgasm system, with modest overlap. Both systems should be taught in every medical school.

Second, physicians should be required to undergo a course in understanding their own sexuality. Research demonstrates doctors will avoid conversations about sex, and it seems to me this could be secondary to being uncomfortable with their own sexuality. After all, to talk with a patient about sex, you cannot be fearful of where the conversation may lead.

Third, the FDA might reconsider the requirements for the approval of drugs for FSD. Currently, to approve a drug for men, an objective finding — ie, an erection — can be sufficient. However, a higher bar, “satisfaction,” which is subjective, must be obtained with women.

Regenerative therapies have proved helpful but are not yet widely adopted; more grant money for the study of regenerative therapies would be a good start here. 

Finally, by the definition of FSD, a woman must be psychologically distressed. The idea of sex is not pleasure alone. Sexual function affects family relationships, emotional health, confidence, even sleep, as well as the emotional well-being of the children who live in the house. Saying women are wonderfully and mysteriously made may be poetic, but it is not an excuse for not learning more and closing the gaps.

Dr. Runels is medical director of the Cellular Medicine Association, Fairhope, Alabama. He reported conflicts of interest with the Cellular Medicine Association, Runels Research Institute, Institute for Lichen Sclerosus, and Vulvar Health. A version of this article first appeared on Medscape.com.

During the month of September, Sexual Health Awareness Month, it may help to notice something: Men and their doctors have significantly more options to help with sexual function than do women and their clinicians. Moreover, the education of physicians regarding the examination and treatment of women for sexual dysfunction has been and remains, even now in 2024, much less thorough than for men. 

Not convinced? Let’s take a quick tour.
 

The New Sexual Revolution and the Growing Anger

Around the time of the release of the book and movie Fifty Shades of Grey, Newsweek put the cultural sensation on its cover.

I bought the magazine at the airport and, while waiting for my plane, showed the story to a woman sitting next to me. “What do you think — is this the new ‘sexual revolution’?” I asked her.

She glanced at the cover and answered as accurately as if she had written the article: “In the ’60s, it became okay for women to have sex; now, it’s okay for women to demand good sex.”

I would add to that: Women are demanding good sex, and they want to define for themselves what “good” means.

That social revolution rages, still.

You would think that the demand would bring a corresponding response in clinical medicine. You would be wrong. Although efforts in some sectors are heroic, overall, the results are lagging the forward movement of women wanting better sex.
 

The Lag in Sexual Education

To examine the progression of the education of physicians regarding the treatment of female sexual dysfunction (FSD), Codispoti and colleagues examined the curricula of seven medical schools in and around Chicago. They found the following: Only one institution identified all anatomic components of the clitoris — one! Four of the seven discussed the physiology of the female orgasm. Only three of the seven highlighted the prevalence and epidemiology of FSD or the treatments for FSD. Only one of the seven explained how to do a genitourinary physical exam specific to assessing FSD. 

When assessing obstetrics and gynecology clinical materials, sexual pleasure, arousal, and libido were not included anywhere in the curricula.

I have been teaching physicians about the therapies I developed (over 5000 clinicians in 50-plus countries over the past 14 years). During those sessions, I often stop the class and ask, “Who in here was taught how to retract the foreskin and examine the penis for phimosis?”

All hands will go up.

Then I will ask, “Who in here was taught in medical school how to retract the clitoral hood and examine the clitoris for phimosis?”

Not once has anyone raised a hand.
 

The Sex Remedies Gap

When I first published research offering support for using platelet-rich plasma to improve sexual function in women, women had not one drug approved by the US Food and Drug Administration (FDA) for the treatment of sexual dysfunction — none. Men had over 20. Today, men have a growing number of FDA-approved drugs for erectile dysfunction, including the “fils”; women have three. 

Women have access to only one FDA-approved medication that primarily affects the genitalia: prasterone. This drug is indicated only for the treatment of pain in postmenopausal women. It does not directly enhance desire or improve orgasms. Said another way, although the incidence of sexual dysfunction is higher in premenopausal women than in other groups, they do not have a single approved medication designed to improve the function of their genitalia. 

The other two of the three available drugs — flibanserin and bremelanotide — primarily affect the brain and could accurately be called psychoactive agents. They are available only for premenopausal women to improve desire. Flibanserin resulted in one extra sexual encounter per month on average, and patients are advised to avoid alcohol while using the drug. The other can make you vomit.

I do think all three of these treatments can be of great help to some women. I am not advising their disappearance. But in contrast to what is available to men, they are woefully inadequate.
 

Historical Perspective

In 1980, the medical establishment believed “most instances of acquired impotence are psychogenic.” Then, with the accidental discovery of the benefits of phosphodiesterase type 5 inhibitors, we realized that most cases of male sexual dysfunction involve the vasculature of the genitalia, not the neuroses of the brain. Yet, our two FDA-approved drugs for women with sexual dysfunction are designed to affect the brain. Women have nothing but off-label therapies to improve the function of the genitalia.

Despite the fact research supports the use of testosterone in women for both libido and orgasm, and despite the fact millions of women are treated with testosterone off-label for the benefit of sexual function, the only widely used FDA-approved class of drugs for women that affects testosterone — birth control pills, by blocking pituitary hormone production (the way they prevent pregnancy) — lowers the production of testosterone. 

One might wonder, considering our expanded understanding of the endocrinology of both men and women, at the irony of why it is acceptable to lower the testosterone level of an adolescent girl knowingly, as if her development did not require the hormone (such would never be acceptable in an adolescent male unless sexual transitioning were the goal); yet, we are fearful of giving testosterone to grown women who can no longer make it.
 

Premenopausal Women: An Orphan Population

The concept of “orphan populations” can partially explain the gap in available therapies between men and women.

Women of childbearing age are risky to study; so, with testosterone, for example, it is safer and cheaper for pharmaceutical companies to prove the benefits for men and ride the profits from the off-label use for women. I don’t mean to condemn the manufacturers of testosterone, only to point out the phenomenon of why up to 30% of the prescriptions written by a primary care physician are off-label; off-label use is common among cardiologists (46%); up to 90% of children in the hospital receive at least one off-label drug; and approval of drugs for premenopausal women is more expensive than approval of drugs for men. 
 

What Can Be Done?

The regrettable situation does not reflect evil intent on the part of regulators, educators, or physicians. But the gap between what women want and what medical education and the pharmaceutical-regulatory complex are providing is intolerably wide.

First, I would recommend a standard, required curriculum for the study of female sexual anatomy and function be established and widely adopted by medical schools. The reproductive system contains different components and a different purpose from the orgasm system, with modest overlap. Both systems should be taught in every medical school.

Second, physicians should be required to undergo a course in understanding their own sexuality. Research demonstrates doctors will avoid conversations about sex, and it seems to me this could be secondary to being uncomfortable with their own sexuality. After all, to talk with a patient about sex, you cannot be fearful of where the conversation may lead.

Third, the FDA might reconsider the requirements for the approval of drugs for FSD. Currently, to approve a drug for men, an objective finding — ie, an erection — can be sufficient. However, a higher bar, “satisfaction,” which is subjective, must be obtained with women.

Regenerative therapies have proved helpful but are not yet widely adopted; more grant money for the study of regenerative therapies would be a good start here. 

Finally, by the definition of FSD, a woman must be psychologically distressed. The idea of sex is not pleasure alone. Sexual function affects family relationships, emotional health, confidence, even sleep, as well as the emotional well-being of the children who live in the house. Saying women are wonderfully and mysteriously made may be poetic, but it is not an excuse for not learning more and closing the gaps.

Dr. Runels is medical director of the Cellular Medicine Association, Fairhope, Alabama. He reported conflicts of interest with the Cellular Medicine Association, Runels Research Institute, Institute for Lichen Sclerosus, and Vulvar Health. A version of this article first appeared on Medscape.com.

How many weeks of vacation do you take each year? Does it feel like enough? What prevents you from taking more time off? Is it a contractual obligation to your employer? Or a concern about the lack of income while your are away? Is it the difficulty of finding coverage for your patient care responsibilities? How much of it is the dread of facing your unattended or poorly attended EHR box when you return?

A recent survey of more than 3000 US physicians found that almost 60% took 3 weeks or less vacation per year? The investigators also learned that 70% of the respondents did patient-related tasks while they were on vacation and less than half had full EHR coverage while they were away. Not surprisingly, providers who expressed concerns about finding someone to cover clinical responsibilities and financial concerns were less likely to take more than 3 weeks’ vacation.

As one might hope, taking more than 3 weeks’ vacation and having full EHR coverage were associated with decreased rates of burnout. On the other hand, spending more than 30 minutes per day doing patient-related work while on vacation was associated with higher rates of burnout.

In their conclusion, the authors suggest that if we hope to reduce physician burnout, employers should introduce system-level initiatives to ensure that physicians take adequate vacation and have adequate coverage for their clinical responsibilities — including EHR inbox management.

I will readily admit that I was one of those physicians who took less than 3 weeks of vacation and can’t recall ever taking more than 2 weeks. Since most of our vacations were staycations, I would usually round on the newborns first thing in the morning when I was in town to keep the flow of new patients coming into the practice.

I’m sure there was some collateral damage to my family, but our children continue to reassure me that they weren’t envious of their peers who went away on “real” vacations. As adults two of them take their families on the kind of vacations that make me envious. The third has married someone who shares, what I might call, a “robust commitment” to showing up in the office. But they seem to be a happy couple.

At the root of my vacation style was an egotistical delusion that there weren’t any clinicians in the community who could look after my patients as well as I did. Unfortunately, I had done little to discourage those patients who shared my distorted view.

I was lucky to have spent nearly all my career without the added burden of an EHR inbox. However, in the lead up to our infrequent vacations, the rush to tie up the loose ends of those patients for whom we had not achieved diagnostic closure was stressful and time consuming. Luckily, as a primary care pediatrician most of their problems were short lived. But, leaving the ship battened down could be exhausting.

I can fully understand why the physicians who are taking less than 3 weeks’ vacation and continue to be burdened by patient-related tasks while they are “away” are more likely to experience burnout. However, I wonder why I seemed to have been resistant considering my vacation style, which the authors of the above-mentioned article feel would have placed me at high risk.

I think the answer may lie in my commitment to making decisions that allowed me to maintain equilibrium in my life. In other words, if there were things in my day-to-day activities that were so taxing or distasteful that I am counting the hours and days until I can escape them, then I needed to make the necessary changes promptly and not count on a vacation to repair the accumulating damage. That may have required cutting back some responsibilities or it may have meant that I needed to be in better mental and physical shape to be able to maintain that equilibrium. Maybe it was more sleep, more exercise, less television, not investing as much in time-wasting meetings. This doesn’t mean that I didn’t have bad days. Stuff happens. But if I was putting together two or three bad days a week, something had to change. A vacation wasn’t going solve the inherent or systemic problems that are making day-to-day life so intolerable that I needed to escape for some respite.

In full disclosure, I will share that at age 55 I took a leave of 2 1/2 months and with my wife and another couple bicycled across America. This was a goal I had harbored since childhood and in anticipation over several decades had banked considerable coverage equity by doing extra coverage for other providers to minimize my guilt feelings at being away. This was not an escape from I job I didn’t enjoy going to everyday. It was an exercise in goal fulfillment.

I think the authors of this recent study should be applauded for providing some numbers to support the obvious. However, if we are looking for ways to minimize physician burnout, we should be giving more attention to the factors in clinical practice that are making it so intolerable. More vacation time is just one strategy.

Encouraging a clinician to take a bit more vacation may help. But, having someone to properly manage the EHR inbox would do a lot more. If your coverage is telling everyone to “Wait until Dr. Away has returned” it is only going to make things worse.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

How many weeks of vacation do you take each year? Does it feel like enough? What prevents you from taking more time off? Is it a contractual obligation to your employer? Or a concern about the lack of income while your are away? Is it the difficulty of finding coverage for your patient care responsibilities? How much of it is the dread of facing your unattended or poorly attended EHR box when you return?

A recent survey of more than 3000 US physicians found that almost 60% took 3 weeks or less vacation per year? The investigators also learned that 70% of the respondents did patient-related tasks while they were on vacation and less than half had full EHR coverage while they were away. Not surprisingly, providers who expressed concerns about finding someone to cover clinical responsibilities and financial concerns were less likely to take more than 3 weeks’ vacation.

As one might hope, taking more than 3 weeks’ vacation and having full EHR coverage were associated with decreased rates of burnout. On the other hand, spending more than 30 minutes per day doing patient-related work while on vacation was associated with higher rates of burnout.

In their conclusion, the authors suggest that if we hope to reduce physician burnout, employers should introduce system-level initiatives to ensure that physicians take adequate vacation and have adequate coverage for their clinical responsibilities — including EHR inbox management.

I will readily admit that I was one of those physicians who took less than 3 weeks of vacation and can’t recall ever taking more than 2 weeks. Since most of our vacations were staycations, I would usually round on the newborns first thing in the morning when I was in town to keep the flow of new patients coming into the practice.

I’m sure there was some collateral damage to my family, but our children continue to reassure me that they weren’t envious of their peers who went away on “real” vacations. As adults two of them take their families on the kind of vacations that make me envious. The third has married someone who shares, what I might call, a “robust commitment” to showing up in the office. But they seem to be a happy couple.

At the root of my vacation style was an egotistical delusion that there weren’t any clinicians in the community who could look after my patients as well as I did. Unfortunately, I had done little to discourage those patients who shared my distorted view.

I was lucky to have spent nearly all my career without the added burden of an EHR inbox. However, in the lead up to our infrequent vacations, the rush to tie up the loose ends of those patients for whom we had not achieved diagnostic closure was stressful and time consuming. Luckily, as a primary care pediatrician most of their problems were short lived. But, leaving the ship battened down could be exhausting.

I can fully understand why the physicians who are taking less than 3 weeks’ vacation and continue to be burdened by patient-related tasks while they are “away” are more likely to experience burnout. However, I wonder why I seemed to have been resistant considering my vacation style, which the authors of the above-mentioned article feel would have placed me at high risk.

I think the answer may lie in my commitment to making decisions that allowed me to maintain equilibrium in my life. In other words, if there were things in my day-to-day activities that were so taxing or distasteful that I am counting the hours and days until I can escape them, then I needed to make the necessary changes promptly and not count on a vacation to repair the accumulating damage. That may have required cutting back some responsibilities or it may have meant that I needed to be in better mental and physical shape to be able to maintain that equilibrium. Maybe it was more sleep, more exercise, less television, not investing as much in time-wasting meetings. This doesn’t mean that I didn’t have bad days. Stuff happens. But if I was putting together two or three bad days a week, something had to change. A vacation wasn’t going solve the inherent or systemic problems that are making day-to-day life so intolerable that I needed to escape for some respite.

In full disclosure, I will share that at age 55 I took a leave of 2 1/2 months and with my wife and another couple bicycled across America. This was a goal I had harbored since childhood and in anticipation over several decades had banked considerable coverage equity by doing extra coverage for other providers to minimize my guilt feelings at being away. This was not an escape from I job I didn’t enjoy going to everyday. It was an exercise in goal fulfillment.

I think the authors of this recent study should be applauded for providing some numbers to support the obvious. However, if we are looking for ways to minimize physician burnout, we should be giving more attention to the factors in clinical practice that are making it so intolerable. More vacation time is just one strategy.

Encouraging a clinician to take a bit more vacation may help. But, having someone to properly manage the EHR inbox would do a lot more. If your coverage is telling everyone to “Wait until Dr. Away has returned” it is only going to make things worse.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

How many weeks of vacation do you take each year? Does it feel like enough? What prevents you from taking more time off? Is it a contractual obligation to your employer? Or a concern about the lack of income while your are away? Is it the difficulty of finding coverage for your patient care responsibilities? How much of it is the dread of facing your unattended or poorly attended EHR box when you return?

A recent survey of more than 3000 US physicians found that almost 60% took 3 weeks or less vacation per year? The investigators also learned that 70% of the respondents did patient-related tasks while they were on vacation and less than half had full EHR coverage while they were away. Not surprisingly, providers who expressed concerns about finding someone to cover clinical responsibilities and financial concerns were less likely to take more than 3 weeks’ vacation.

As one might hope, taking more than 3 weeks’ vacation and having full EHR coverage were associated with decreased rates of burnout. On the other hand, spending more than 30 minutes per day doing patient-related work while on vacation was associated with higher rates of burnout.

In their conclusion, the authors suggest that if we hope to reduce physician burnout, employers should introduce system-level initiatives to ensure that physicians take adequate vacation and have adequate coverage for their clinical responsibilities — including EHR inbox management.

I will readily admit that I was one of those physicians who took less than 3 weeks of vacation and can’t recall ever taking more than 2 weeks. Since most of our vacations were staycations, I would usually round on the newborns first thing in the morning when I was in town to keep the flow of new patients coming into the practice.

I’m sure there was some collateral damage to my family, but our children continue to reassure me that they weren’t envious of their peers who went away on “real” vacations. As adults two of them take their families on the kind of vacations that make me envious. The third has married someone who shares, what I might call, a “robust commitment” to showing up in the office. But they seem to be a happy couple.

At the root of my vacation style was an egotistical delusion that there weren’t any clinicians in the community who could look after my patients as well as I did. Unfortunately, I had done little to discourage those patients who shared my distorted view.

I was lucky to have spent nearly all my career without the added burden of an EHR inbox. However, in the lead up to our infrequent vacations, the rush to tie up the loose ends of those patients for whom we had not achieved diagnostic closure was stressful and time consuming. Luckily, as a primary care pediatrician most of their problems were short lived. But, leaving the ship battened down could be exhausting.

I can fully understand why the physicians who are taking less than 3 weeks’ vacation and continue to be burdened by patient-related tasks while they are “away” are more likely to experience burnout. However, I wonder why I seemed to have been resistant considering my vacation style, which the authors of the above-mentioned article feel would have placed me at high risk.

I think the answer may lie in my commitment to making decisions that allowed me to maintain equilibrium in my life. In other words, if there were things in my day-to-day activities that were so taxing or distasteful that I am counting the hours and days until I can escape them, then I needed to make the necessary changes promptly and not count on a vacation to repair the accumulating damage. That may have required cutting back some responsibilities or it may have meant that I needed to be in better mental and physical shape to be able to maintain that equilibrium. Maybe it was more sleep, more exercise, less television, not investing as much in time-wasting meetings. This doesn’t mean that I didn’t have bad days. Stuff happens. But if I was putting together two or three bad days a week, something had to change. A vacation wasn’t going solve the inherent or systemic problems that are making day-to-day life so intolerable that I needed to escape for some respite.

In full disclosure, I will share that at age 55 I took a leave of 2 1/2 months and with my wife and another couple bicycled across America. This was a goal I had harbored since childhood and in anticipation over several decades had banked considerable coverage equity by doing extra coverage for other providers to minimize my guilt feelings at being away. This was not an escape from I job I didn’t enjoy going to everyday. It was an exercise in goal fulfillment.

I think the authors of this recent study should be applauded for providing some numbers to support the obvious. However, if we are looking for ways to minimize physician burnout, we should be giving more attention to the factors in clinical practice that are making it so intolerable. More vacation time is just one strategy.

Encouraging a clinician to take a bit more vacation may help. But, having someone to properly manage the EHR inbox would do a lot more. If your coverage is telling everyone to “Wait until Dr. Away has returned” it is only going to make things worse.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Digital pathology assisted by artificial intelligence (AI) has the potential to transform the diagnosis and treatment of fibrotic liver disease in the next few years and to reshape clinical trials, clearing the way for new therapies.

Although the technology is not yet approved for routine clinical use, it’s constantly improving and aims to address the limitations inherent in today’s pathology processes.

“You do a biopsy, but instead of having a pathologist read it with their very rough scores of stage 1, 2, or 3, you read it by an AI-driven machine that can quantify it with a score of 1.5 or 1.75 instead of 1 or 2,” Vlad Ratziu, MD, PhD, professor of hepatology at the Sorbonne Université and Hôpital Pitié-Salpêtrière Medical School in Paris, France, and coeditor of The Journal of Hepatology, said in an interview.

“The technology is automated, more sensitive to change, and more highly quantitative. It has implications for liver disease diagnoses, clinical trials, and treatments,” added Dr. Ratziu, who has written about the promise and challenges inherent in developing treatments for metabolic dysfunction–associated steatotic liver disease (MASLD).

To explore the potential impact of AI-powered technologies for the clinic, this news organization spoke with representatives from three companies identified by Dr. Ratziu as leaders in the field: HistoIndex, PathAI, and PharmaNest. Each company uses proprietary technology augmented by AI, and their tools have been used in published trials.
 

Moving Toward Better Diagnoses and Disease Management

The traditional approach for staging liver fibrosis relies on trained pathologists manually evaluating stained tissue samples obtained from biopsies of the liver.

But this method, though still considered the gold standard, doesn’t always provide the granularity needed for an accurate diagnosis or a reliable assessment in clinical trials, said Dean Tai, PhD, HistoIndex’s cofounder and chief scientific officer.

Although noninvasive tests (NITs), alone or with traditional histologic examination, are increasingly used during clinical management because they are less invasive and more repeatable for disease monitoring, they are limited in their precision and ability to provide comprehensive information, Dr. Tai said. That’s because “no single NIT or single-dimensional measurement of a biomarker offers a full assessment of disease activity, fibrogenic drive, and fibrosis load.”

In contrast, AI provides “a highly reproducible and objective assessment of liver fibrosis severity,” he said. “It eliminates the variability associated with staining methods, while revealing changes in the nano-architecture and morphology of collagen fibers not discernible by the human eye or current NITs, especially in the early stages of fibrosis or in cases of simultaneous progression and regression.”

Mathieu Petitjean, PhD, founder and CEO of PharmaNest, has a similar view. 

Although degree of liver fibrosis is associated with long-term outcomes of patients with MASLD, “poor detection thresholds due to their categorical nature mean that small and relevant changes are not reflected by changes in staging,” he said. “The reliable detection [with AI] of subtle changes in the phenotypes of fibrosis will significantly enrich the understanding of progression and regression of fibrosis severity.”

The ability of AI-based tools to see patterns the human eye cannot also means they could “help in predicting which patient may respond to a drug, in order to get the right treatments to the right patients as soon as possible,” said Katy Wack, PhD, vice president of clinical development at PathAI.

“Additionally, AI-based algorithms have been developed to provide more quantitative continuous scores to better capture change and discover new tissue-based biomarkers, which may be prognostic or predictive of clinical benefit,” she said. 

Such tools are currently undergoing testing and validation for use in trials and diagnostically.

The standardization and reproducibility offered by AI-driven technology could facilitate more consistent diagnoses across different healthcare settings, Dr. Tai suggested. “As the integration of the technology with other blood-, imaging-, and omics-based techniques evolves, it may enable earlier detection of liver diseases, more accurate monitoring of disease progression, and better evaluation of treatment responses, ultimately improving patient care and outcomes.”
 

More Effective Clinical Trials

The limitations of conventional pathology may be responsible, at least in part, for the repeated failure of novel compounds to move from phase 2 to phase 3 clinical trials, and from clinical trials to approval, the sources agreed.

“In clinical trials, patients are subject to enrollment criteria using liver biopsies, which are scored with a composite scoring system involving four different histologic components to grade and stage the disease,” Dr. Wack noted. 

However, there is wide variability between pathologists on biopsy scoring, and an individual pathologist presented with the same sample may give it a different score after some time has passed, she said.

That means “we are using a nonstandardized and inconsistent scoring system to determine whether a patient can be enrolled or not into a trial,” Dr. Wack said. 

The change in the composite score over a follow-up period, usually 1-2 years, determines whether a patient has responded to the candidate drug and, ultimately, whether that drug could be considered for approval, Dr. Wack said.

Because scores at the baseline and follow-up timepoints are not precise and inconsistent across pathologist readers, and even the same reader over time, there are often many “false-positive” and “false-negative” responses that can result in potential therapeutics either failing or succeeding in clinical trials, she said.

To address this variability in biopsy scoring as it relates to clinical trials, regulatory bodies have recommended a consensus approach, in which multiple pathologists read the same biopsy independently and a median score is used, or pathologists convene to come to an agreement, Dr. Wack said. 

“This is a very costly and burdensome approach and is still subject to interconsensus panel variation,” she said.

The introduction of digital pathology using validated digital viewers, where pathologists can view a glass slide digitally and pan and zoom over the image as they can with a microscope, means that many pathologists can read the same slide in parallel, she explained.

“If they need to discuss, they can do so efficiently over a phone call, each using their own computer screen and shared annotation tools to facilitate their discussion.”

Although this consensus approach can improve consistency, it still leads to variability in scoring across different groups of pathologists, Dr. Wack said.

This is where AI-assisted pathology comes into play.

“With this approach, a pathologist still views the image digitally, but an algorithm has predicted and highlighted key features and recommended quantitative scores,” she said.

This approach has been shown to increase precision for pathologists, thereby increasing reproducibility and standardizing scoring across timepoints and clinical trials.
 

What’s Ahead

These AI tools could address pathology’s lack of scalability, the result of a limited number of trained pathologists capable of doing liver biopsy assessments, Dr. Tai said. 

“Digital pathology workflows enable the transformation of conventional histologic glass slides into large digital images using scanners, allowing significant productivity gains in terms of workflow and collaboration,” he said.

Although AI-assisted pathology tools are still being validated, their promise for improving diagnoses and uncovering new treatments is clear, the interviewees agreed.

Extending its use to stage fibrosis in other liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and alcoholic liver disease, is also in progress on an experimental basis but will take time to validate.

“The landscape will evolve quickly in the coming 3-4 years,” Dr. Petitjean predicted. “To start, their intended use will likely be limited to a decision-support tool to enhance the performance of pathologists and perhaps stratify or triage cases sent for routine vs expert review.”

Dr. Petitjean even suggested that the increasing role of NITs and the amount of data being generated prospectively and retrospectively around liver biomarkers could mean that liver biopsies might not be needed one day.

A version of this article appeared on Medscape.com.

Digital pathology assisted by artificial intelligence (AI) has the potential to transform the diagnosis and treatment of fibrotic liver disease in the next few years and to reshape clinical trials, clearing the way for new therapies.

Although the technology is not yet approved for routine clinical use, it’s constantly improving and aims to address the limitations inherent in today’s pathology processes.

“You do a biopsy, but instead of having a pathologist read it with their very rough scores of stage 1, 2, or 3, you read it by an AI-driven machine that can quantify it with a score of 1.5 or 1.75 instead of 1 or 2,” Vlad Ratziu, MD, PhD, professor of hepatology at the Sorbonne Université and Hôpital Pitié-Salpêtrière Medical School in Paris, France, and coeditor of The Journal of Hepatology, said in an interview.

“The technology is automated, more sensitive to change, and more highly quantitative. It has implications for liver disease diagnoses, clinical trials, and treatments,” added Dr. Ratziu, who has written about the promise and challenges inherent in developing treatments for metabolic dysfunction–associated steatotic liver disease (MASLD).

To explore the potential impact of AI-powered technologies for the clinic, this news organization spoke with representatives from three companies identified by Dr. Ratziu as leaders in the field: HistoIndex, PathAI, and PharmaNest. Each company uses proprietary technology augmented by AI, and their tools have been used in published trials.
 

Moving Toward Better Diagnoses and Disease Management

The traditional approach for staging liver fibrosis relies on trained pathologists manually evaluating stained tissue samples obtained from biopsies of the liver.

But this method, though still considered the gold standard, doesn’t always provide the granularity needed for an accurate diagnosis or a reliable assessment in clinical trials, said Dean Tai, PhD, HistoIndex’s cofounder and chief scientific officer.

Although noninvasive tests (NITs), alone or with traditional histologic examination, are increasingly used during clinical management because they are less invasive and more repeatable for disease monitoring, they are limited in their precision and ability to provide comprehensive information, Dr. Tai said. That’s because “no single NIT or single-dimensional measurement of a biomarker offers a full assessment of disease activity, fibrogenic drive, and fibrosis load.”

In contrast, AI provides “a highly reproducible and objective assessment of liver fibrosis severity,” he said. “It eliminates the variability associated with staining methods, while revealing changes in the nano-architecture and morphology of collagen fibers not discernible by the human eye or current NITs, especially in the early stages of fibrosis or in cases of simultaneous progression and regression.”

Mathieu Petitjean, PhD, founder and CEO of PharmaNest, has a similar view. 

Although degree of liver fibrosis is associated with long-term outcomes of patients with MASLD, “poor detection thresholds due to their categorical nature mean that small and relevant changes are not reflected by changes in staging,” he said. “The reliable detection [with AI] of subtle changes in the phenotypes of fibrosis will significantly enrich the understanding of progression and regression of fibrosis severity.”

The ability of AI-based tools to see patterns the human eye cannot also means they could “help in predicting which patient may respond to a drug, in order to get the right treatments to the right patients as soon as possible,” said Katy Wack, PhD, vice president of clinical development at PathAI.

“Additionally, AI-based algorithms have been developed to provide more quantitative continuous scores to better capture change and discover new tissue-based biomarkers, which may be prognostic or predictive of clinical benefit,” she said. 

Such tools are currently undergoing testing and validation for use in trials and diagnostically.

The standardization and reproducibility offered by AI-driven technology could facilitate more consistent diagnoses across different healthcare settings, Dr. Tai suggested. “As the integration of the technology with other blood-, imaging-, and omics-based techniques evolves, it may enable earlier detection of liver diseases, more accurate monitoring of disease progression, and better evaluation of treatment responses, ultimately improving patient care and outcomes.”
 

More Effective Clinical Trials

The limitations of conventional pathology may be responsible, at least in part, for the repeated failure of novel compounds to move from phase 2 to phase 3 clinical trials, and from clinical trials to approval, the sources agreed.

“In clinical trials, patients are subject to enrollment criteria using liver biopsies, which are scored with a composite scoring system involving four different histologic components to grade and stage the disease,” Dr. Wack noted. 

However, there is wide variability between pathologists on biopsy scoring, and an individual pathologist presented with the same sample may give it a different score after some time has passed, she said.

That means “we are using a nonstandardized and inconsistent scoring system to determine whether a patient can be enrolled or not into a trial,” Dr. Wack said. 

The change in the composite score over a follow-up period, usually 1-2 years, determines whether a patient has responded to the candidate drug and, ultimately, whether that drug could be considered for approval, Dr. Wack said.

Because scores at the baseline and follow-up timepoints are not precise and inconsistent across pathologist readers, and even the same reader over time, there are often many “false-positive” and “false-negative” responses that can result in potential therapeutics either failing or succeeding in clinical trials, she said.

To address this variability in biopsy scoring as it relates to clinical trials, regulatory bodies have recommended a consensus approach, in which multiple pathologists read the same biopsy independently and a median score is used, or pathologists convene to come to an agreement, Dr. Wack said. 

“This is a very costly and burdensome approach and is still subject to interconsensus panel variation,” she said.

The introduction of digital pathology using validated digital viewers, where pathologists can view a glass slide digitally and pan and zoom over the image as they can with a microscope, means that many pathologists can read the same slide in parallel, she explained.

“If they need to discuss, they can do so efficiently over a phone call, each using their own computer screen and shared annotation tools to facilitate their discussion.”

Although this consensus approach can improve consistency, it still leads to variability in scoring across different groups of pathologists, Dr. Wack said.

This is where AI-assisted pathology comes into play.

“With this approach, a pathologist still views the image digitally, but an algorithm has predicted and highlighted key features and recommended quantitative scores,” she said.

This approach has been shown to increase precision for pathologists, thereby increasing reproducibility and standardizing scoring across timepoints and clinical trials.
 

What’s Ahead

These AI tools could address pathology’s lack of scalability, the result of a limited number of trained pathologists capable of doing liver biopsy assessments, Dr. Tai said. 

“Digital pathology workflows enable the transformation of conventional histologic glass slides into large digital images using scanners, allowing significant productivity gains in terms of workflow and collaboration,” he said.

Although AI-assisted pathology tools are still being validated, their promise for improving diagnoses and uncovering new treatments is clear, the interviewees agreed.

Extending its use to stage fibrosis in other liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and alcoholic liver disease, is also in progress on an experimental basis but will take time to validate.

“The landscape will evolve quickly in the coming 3-4 years,” Dr. Petitjean predicted. “To start, their intended use will likely be limited to a decision-support tool to enhance the performance of pathologists and perhaps stratify or triage cases sent for routine vs expert review.”

Dr. Petitjean even suggested that the increasing role of NITs and the amount of data being generated prospectively and retrospectively around liver biomarkers could mean that liver biopsies might not be needed one day.

A version of this article appeared on Medscape.com.

Digital pathology assisted by artificial intelligence (AI) has the potential to transform the diagnosis and treatment of fibrotic liver disease in the next few years and to reshape clinical trials, clearing the way for new therapies.

Although the technology is not yet approved for routine clinical use, it’s constantly improving and aims to address the limitations inherent in today’s pathology processes.

“You do a biopsy, but instead of having a pathologist read it with their very rough scores of stage 1, 2, or 3, you read it by an AI-driven machine that can quantify it with a score of 1.5 or 1.75 instead of 1 or 2,” Vlad Ratziu, MD, PhD, professor of hepatology at the Sorbonne Université and Hôpital Pitié-Salpêtrière Medical School in Paris, France, and coeditor of The Journal of Hepatology, said in an interview.

“The technology is automated, more sensitive to change, and more highly quantitative. It has implications for liver disease diagnoses, clinical trials, and treatments,” added Dr. Ratziu, who has written about the promise and challenges inherent in developing treatments for metabolic dysfunction–associated steatotic liver disease (MASLD).

To explore the potential impact of AI-powered technologies for the clinic, this news organization spoke with representatives from three companies identified by Dr. Ratziu as leaders in the field: HistoIndex, PathAI, and PharmaNest. Each company uses proprietary technology augmented by AI, and their tools have been used in published trials.
 

Moving Toward Better Diagnoses and Disease Management

The traditional approach for staging liver fibrosis relies on trained pathologists manually evaluating stained tissue samples obtained from biopsies of the liver.

But this method, though still considered the gold standard, doesn’t always provide the granularity needed for an accurate diagnosis or a reliable assessment in clinical trials, said Dean Tai, PhD, HistoIndex’s cofounder and chief scientific officer.

Although noninvasive tests (NITs), alone or with traditional histologic examination, are increasingly used during clinical management because they are less invasive and more repeatable for disease monitoring, they are limited in their precision and ability to provide comprehensive information, Dr. Tai said. That’s because “no single NIT or single-dimensional measurement of a biomarker offers a full assessment of disease activity, fibrogenic drive, and fibrosis load.”

In contrast, AI provides “a highly reproducible and objective assessment of liver fibrosis severity,” he said. “It eliminates the variability associated with staining methods, while revealing changes in the nano-architecture and morphology of collagen fibers not discernible by the human eye or current NITs, especially in the early stages of fibrosis or in cases of simultaneous progression and regression.”

Mathieu Petitjean, PhD, founder and CEO of PharmaNest, has a similar view. 

Although degree of liver fibrosis is associated with long-term outcomes of patients with MASLD, “poor detection thresholds due to their categorical nature mean that small and relevant changes are not reflected by changes in staging,” he said. “The reliable detection [with AI] of subtle changes in the phenotypes of fibrosis will significantly enrich the understanding of progression and regression of fibrosis severity.”

The ability of AI-based tools to see patterns the human eye cannot also means they could “help in predicting which patient may respond to a drug, in order to get the right treatments to the right patients as soon as possible,” said Katy Wack, PhD, vice president of clinical development at PathAI.

“Additionally, AI-based algorithms have been developed to provide more quantitative continuous scores to better capture change and discover new tissue-based biomarkers, which may be prognostic or predictive of clinical benefit,” she said. 

Such tools are currently undergoing testing and validation for use in trials and diagnostically.

The standardization and reproducibility offered by AI-driven technology could facilitate more consistent diagnoses across different healthcare settings, Dr. Tai suggested. “As the integration of the technology with other blood-, imaging-, and omics-based techniques evolves, it may enable earlier detection of liver diseases, more accurate monitoring of disease progression, and better evaluation of treatment responses, ultimately improving patient care and outcomes.”
 

More Effective Clinical Trials

The limitations of conventional pathology may be responsible, at least in part, for the repeated failure of novel compounds to move from phase 2 to phase 3 clinical trials, and from clinical trials to approval, the sources agreed.

“In clinical trials, patients are subject to enrollment criteria using liver biopsies, which are scored with a composite scoring system involving four different histologic components to grade and stage the disease,” Dr. Wack noted. 

However, there is wide variability between pathologists on biopsy scoring, and an individual pathologist presented with the same sample may give it a different score after some time has passed, she said.

That means “we are using a nonstandardized and inconsistent scoring system to determine whether a patient can be enrolled or not into a trial,” Dr. Wack said. 

The change in the composite score over a follow-up period, usually 1-2 years, determines whether a patient has responded to the candidate drug and, ultimately, whether that drug could be considered for approval, Dr. Wack said.

Because scores at the baseline and follow-up timepoints are not precise and inconsistent across pathologist readers, and even the same reader over time, there are often many “false-positive” and “false-negative” responses that can result in potential therapeutics either failing or succeeding in clinical trials, she said.

To address this variability in biopsy scoring as it relates to clinical trials, regulatory bodies have recommended a consensus approach, in which multiple pathologists read the same biopsy independently and a median score is used, or pathologists convene to come to an agreement, Dr. Wack said. 

“This is a very costly and burdensome approach and is still subject to interconsensus panel variation,” she said.

The introduction of digital pathology using validated digital viewers, where pathologists can view a glass slide digitally and pan and zoom over the image as they can with a microscope, means that many pathologists can read the same slide in parallel, she explained.

“If they need to discuss, they can do so efficiently over a phone call, each using their own computer screen and shared annotation tools to facilitate their discussion.”

Although this consensus approach can improve consistency, it still leads to variability in scoring across different groups of pathologists, Dr. Wack said.

This is where AI-assisted pathology comes into play.

“With this approach, a pathologist still views the image digitally, but an algorithm has predicted and highlighted key features and recommended quantitative scores,” she said.

This approach has been shown to increase precision for pathologists, thereby increasing reproducibility and standardizing scoring across timepoints and clinical trials.
 

What’s Ahead

These AI tools could address pathology’s lack of scalability, the result of a limited number of trained pathologists capable of doing liver biopsy assessments, Dr. Tai said. 

“Digital pathology workflows enable the transformation of conventional histologic glass slides into large digital images using scanners, allowing significant productivity gains in terms of workflow and collaboration,” he said.

Although AI-assisted pathology tools are still being validated, their promise for improving diagnoses and uncovering new treatments is clear, the interviewees agreed.

Extending its use to stage fibrosis in other liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and alcoholic liver disease, is also in progress on an experimental basis but will take time to validate.

“The landscape will evolve quickly in the coming 3-4 years,” Dr. Petitjean predicted. “To start, their intended use will likely be limited to a decision-support tool to enhance the performance of pathologists and perhaps stratify or triage cases sent for routine vs expert review.”

Dr. Petitjean even suggested that the increasing role of NITs and the amount of data being generated prospectively and retrospectively around liver biomarkers could mean that liver biopsies might not be needed one day.

A version of this article appeared on Medscape.com.