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Leaving ED Without Being Seen Entails Increasing Risks
Higher rates of leaving the emergency department (ED) without being seen are linked to increased short-term mortality or hospitalization, according to a cohort study in Ontario, Canada.
“We found that after 2020, there was a 14% higher risk for death or hospitalization within 7 days” among patients who left without being seen (LWBS), Candace McNaughton, MD, PhD, associate professor of medicine at the University of Toronto and scientist at Sunnybrook Research Institute, both in Toronto, Ontario, Canada, told this news organization.
“When we looked at death by itself, there was a 46% higher risk after 2020,” she said. “Even 30 days after a LWBS ED visit, there was still a 5% increased risk for death/hospitalization and a 24% increased risk for death.”
The study was published in the Journal of the American College of Emergency Physicians Open.
LWBS Rates Increased
Researchers used linked administrative data to analyze temporal trends in monthly rates of ED and LWBS visits for adults in Ontario from 2014 to 2023.
They compared the composite outcome of 7-day all-cause mortality or hospitalization following an LWBS ED visit in April 2022‒March 2023 (recent period) with that following an LWBS ED visit in April 2014‒March 2020 (baseline period), after adjustment for age, sex, and Charlson Comorbidity Index (CCI).
In the two periods, patient characteristics were similar across age, sex, neighborhood-level income quartile, history of being unhoused, rurality, CCI, day, time, and mode of arrival. The median age was 40 years for the baseline period and 42 years for the recent period.
Temporal trends showed sustained increases in monthly LWBS rates after 2020, despite fewer monthly ED visits. The rate of LWBS ED visits after April 1, 2020, exceeded the baseline period’s single-month LWBS maximum of 4% in 15 of 36 months.
The rate of 7-day all-cause mortality or hospitalization was 3.4% in the recent period vs 2.9% in the baseline period (adjusted risk ratio [aRR], 1.14), despite similar rates of post-ED outpatient visits (7-day recent and baseline, 38.9% and 39.7%, respectively).
Similar trends were seen at 30 days for all-cause mortality or hospitalization (6.2% in the recent period vs 5.8% at baseline; aRR, 1.05) despite similar rates of post-ED outpatient visits (59.4% and 59.7%, respectively).
After April 1, 2020, monthly ED visits and the proportion of patients who LWBS varied widely.
The proportion of LWBS visits categorized as emergent on the Canadian Triage and Acuity Scale was higher during the recent period (12.9% vs 9.2% in the baseline period), and fewer visits were categorized as semiurgent (22.6% vs 31.9%, respectively). This finding suggested a higher acuity of illness among patients who LWBS in the recent period.
LWBS Visits ‘Not Benign’
Results of a preplanned subgroup analysis examining the risk for all-cause mortality after an LWBS visit were “particularly notable,” the authors wrote, with a 46% higher adjusted risk for death at 7 days and 24% higher adjusted risk at 30 days.
The observational study had several limitations, however. The authors could not draw conclusions regarding direct causes of the increased risk for severe short-term adverse health outcomes after an LWBS ED visit, and residual confounding is possible. Cause-of-death information was not available to generate hypotheses for future studies of potential causes. Furthermore, the findings may not be generalizable to systems without universal access to healthcare.
Nevertheless, the findings are a “concerning signal [and] should prompt interventions to address system- and population-level causes,” the authors wrote.
“Unfortunately, because of politics, since 2020, ED closures in Ontario have become more and more common and seem to be affecting more and more Ontarians,” said McNaughton. “It would be surprising if ED closure didn’t play some role in our findings.”
She added, “It is important to note that people in our study were relatively young, with a median age in their 40s; this makes our findings all the more concerning. Clinicians should be aware that LWBS ED visits are not necessarily benign, particularly when rates of LWBS ED visits are high.”
Unanswered Questions
The study raised the following questions that the authors are or will be investigating, according to McNaughton:
- Which patients are at greatest risk for bad outcomes if they leave the ED without being seen, and why?
- How much of the findings might be related to recent ED closures, longer ED wait times, or other factors? Are there geographic variations in risk?
- What can be done in the ED to prevent LWBS ED visits, and what can be changed outside the ED to prevent LWBS ED visits? For example, what can hospitals do to reduce boarding in the ED? If patients leave without being seen, should they be contacted to try to meet their health needs in other ways?
- What worked in terms of maintaining access to outpatient medical care, despite the considerable disruptions starting in 2020, and how can continued success be ensured?
To address the current situation, McNaughton said, “We need consistent, predictable, and sustained investment in our public healthcare system. We need long-term, consistent funding for primary care, ED care, as well as hospital and long-term care.”
“It takes years to recruit and train the teams of people necessary to provide the high-quality medical care that Canadians have a right to. There are no shortcuts,” she concluded.
‘Tragic Situation’
American College of Emergency Physicians (ACEP) spokesperson Jesse Pines, MD, chief of clinical innovation at US Acute Care Solutions; clinical professor of emergency medicine at George Washington University in Washington, DC; and professor of emergency medicine at Drexel University in Philadelphia, commented on the study for this news organization.
“Similar to what the authors found in their report, LWBS and other metrics — specifically boarding — have progressively increased in the United States, in particular, since the early part of 2021,” he said. “The primary factor in the US driving this, and one that ACEP is trying to address on a national scale, is the boarding of admitted patients.”
When the number of boarded patients increases, there is less space in the ED for new patients, and waits increase, Pines explained. Some patients leave without being seen, and a subset of those patients experience poor outcomes. “It’s a tragic situation that is worsening.”
“Emergency physicians like me always worry when patients leave without being seen,” he said. While some of those patients have self-limited conditions that will improve on their own, “some have critical life-threatening conditions that require care and hospitalization. The worry is that these patients experience poorer outcomes,” Pines said. “The authors showed that this is increasingly the case in Canada. The same is likely true in the US.”
The study was funded by the Canadian Institutes of Health Research. McNaughton and Pines declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Higher rates of leaving the emergency department (ED) without being seen are linked to increased short-term mortality or hospitalization, according to a cohort study in Ontario, Canada.
“We found that after 2020, there was a 14% higher risk for death or hospitalization within 7 days” among patients who left without being seen (LWBS), Candace McNaughton, MD, PhD, associate professor of medicine at the University of Toronto and scientist at Sunnybrook Research Institute, both in Toronto, Ontario, Canada, told this news organization.
“When we looked at death by itself, there was a 46% higher risk after 2020,” she said. “Even 30 days after a LWBS ED visit, there was still a 5% increased risk for death/hospitalization and a 24% increased risk for death.”
The study was published in the Journal of the American College of Emergency Physicians Open.
LWBS Rates Increased
Researchers used linked administrative data to analyze temporal trends in monthly rates of ED and LWBS visits for adults in Ontario from 2014 to 2023.
They compared the composite outcome of 7-day all-cause mortality or hospitalization following an LWBS ED visit in April 2022‒March 2023 (recent period) with that following an LWBS ED visit in April 2014‒March 2020 (baseline period), after adjustment for age, sex, and Charlson Comorbidity Index (CCI).
In the two periods, patient characteristics were similar across age, sex, neighborhood-level income quartile, history of being unhoused, rurality, CCI, day, time, and mode of arrival. The median age was 40 years for the baseline period and 42 years for the recent period.
Temporal trends showed sustained increases in monthly LWBS rates after 2020, despite fewer monthly ED visits. The rate of LWBS ED visits after April 1, 2020, exceeded the baseline period’s single-month LWBS maximum of 4% in 15 of 36 months.
The rate of 7-day all-cause mortality or hospitalization was 3.4% in the recent period vs 2.9% in the baseline period (adjusted risk ratio [aRR], 1.14), despite similar rates of post-ED outpatient visits (7-day recent and baseline, 38.9% and 39.7%, respectively).
Similar trends were seen at 30 days for all-cause mortality or hospitalization (6.2% in the recent period vs 5.8% at baseline; aRR, 1.05) despite similar rates of post-ED outpatient visits (59.4% and 59.7%, respectively).
After April 1, 2020, monthly ED visits and the proportion of patients who LWBS varied widely.
The proportion of LWBS visits categorized as emergent on the Canadian Triage and Acuity Scale was higher during the recent period (12.9% vs 9.2% in the baseline period), and fewer visits were categorized as semiurgent (22.6% vs 31.9%, respectively). This finding suggested a higher acuity of illness among patients who LWBS in the recent period.
LWBS Visits ‘Not Benign’
Results of a preplanned subgroup analysis examining the risk for all-cause mortality after an LWBS visit were “particularly notable,” the authors wrote, with a 46% higher adjusted risk for death at 7 days and 24% higher adjusted risk at 30 days.
The observational study had several limitations, however. The authors could not draw conclusions regarding direct causes of the increased risk for severe short-term adverse health outcomes after an LWBS ED visit, and residual confounding is possible. Cause-of-death information was not available to generate hypotheses for future studies of potential causes. Furthermore, the findings may not be generalizable to systems without universal access to healthcare.
Nevertheless, the findings are a “concerning signal [and] should prompt interventions to address system- and population-level causes,” the authors wrote.
“Unfortunately, because of politics, since 2020, ED closures in Ontario have become more and more common and seem to be affecting more and more Ontarians,” said McNaughton. “It would be surprising if ED closure didn’t play some role in our findings.”
She added, “It is important to note that people in our study were relatively young, with a median age in their 40s; this makes our findings all the more concerning. Clinicians should be aware that LWBS ED visits are not necessarily benign, particularly when rates of LWBS ED visits are high.”
Unanswered Questions
The study raised the following questions that the authors are or will be investigating, according to McNaughton:
- Which patients are at greatest risk for bad outcomes if they leave the ED without being seen, and why?
- How much of the findings might be related to recent ED closures, longer ED wait times, or other factors? Are there geographic variations in risk?
- What can be done in the ED to prevent LWBS ED visits, and what can be changed outside the ED to prevent LWBS ED visits? For example, what can hospitals do to reduce boarding in the ED? If patients leave without being seen, should they be contacted to try to meet their health needs in other ways?
- What worked in terms of maintaining access to outpatient medical care, despite the considerable disruptions starting in 2020, and how can continued success be ensured?
To address the current situation, McNaughton said, “We need consistent, predictable, and sustained investment in our public healthcare system. We need long-term, consistent funding for primary care, ED care, as well as hospital and long-term care.”
“It takes years to recruit and train the teams of people necessary to provide the high-quality medical care that Canadians have a right to. There are no shortcuts,” she concluded.
‘Tragic Situation’
American College of Emergency Physicians (ACEP) spokesperson Jesse Pines, MD, chief of clinical innovation at US Acute Care Solutions; clinical professor of emergency medicine at George Washington University in Washington, DC; and professor of emergency medicine at Drexel University in Philadelphia, commented on the study for this news organization.
“Similar to what the authors found in their report, LWBS and other metrics — specifically boarding — have progressively increased in the United States, in particular, since the early part of 2021,” he said. “The primary factor in the US driving this, and one that ACEP is trying to address on a national scale, is the boarding of admitted patients.”
When the number of boarded patients increases, there is less space in the ED for new patients, and waits increase, Pines explained. Some patients leave without being seen, and a subset of those patients experience poor outcomes. “It’s a tragic situation that is worsening.”
“Emergency physicians like me always worry when patients leave without being seen,” he said. While some of those patients have self-limited conditions that will improve on their own, “some have critical life-threatening conditions that require care and hospitalization. The worry is that these patients experience poorer outcomes,” Pines said. “The authors showed that this is increasingly the case in Canada. The same is likely true in the US.”
The study was funded by the Canadian Institutes of Health Research. McNaughton and Pines declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Higher rates of leaving the emergency department (ED) without being seen are linked to increased short-term mortality or hospitalization, according to a cohort study in Ontario, Canada.
“We found that after 2020, there was a 14% higher risk for death or hospitalization within 7 days” among patients who left without being seen (LWBS), Candace McNaughton, MD, PhD, associate professor of medicine at the University of Toronto and scientist at Sunnybrook Research Institute, both in Toronto, Ontario, Canada, told this news organization.
“When we looked at death by itself, there was a 46% higher risk after 2020,” she said. “Even 30 days after a LWBS ED visit, there was still a 5% increased risk for death/hospitalization and a 24% increased risk for death.”
The study was published in the Journal of the American College of Emergency Physicians Open.
LWBS Rates Increased
Researchers used linked administrative data to analyze temporal trends in monthly rates of ED and LWBS visits for adults in Ontario from 2014 to 2023.
They compared the composite outcome of 7-day all-cause mortality or hospitalization following an LWBS ED visit in April 2022‒March 2023 (recent period) with that following an LWBS ED visit in April 2014‒March 2020 (baseline period), after adjustment for age, sex, and Charlson Comorbidity Index (CCI).
In the two periods, patient characteristics were similar across age, sex, neighborhood-level income quartile, history of being unhoused, rurality, CCI, day, time, and mode of arrival. The median age was 40 years for the baseline period and 42 years for the recent period.
Temporal trends showed sustained increases in monthly LWBS rates after 2020, despite fewer monthly ED visits. The rate of LWBS ED visits after April 1, 2020, exceeded the baseline period’s single-month LWBS maximum of 4% in 15 of 36 months.
The rate of 7-day all-cause mortality or hospitalization was 3.4% in the recent period vs 2.9% in the baseline period (adjusted risk ratio [aRR], 1.14), despite similar rates of post-ED outpatient visits (7-day recent and baseline, 38.9% and 39.7%, respectively).
Similar trends were seen at 30 days for all-cause mortality or hospitalization (6.2% in the recent period vs 5.8% at baseline; aRR, 1.05) despite similar rates of post-ED outpatient visits (59.4% and 59.7%, respectively).
After April 1, 2020, monthly ED visits and the proportion of patients who LWBS varied widely.
The proportion of LWBS visits categorized as emergent on the Canadian Triage and Acuity Scale was higher during the recent period (12.9% vs 9.2% in the baseline period), and fewer visits were categorized as semiurgent (22.6% vs 31.9%, respectively). This finding suggested a higher acuity of illness among patients who LWBS in the recent period.
LWBS Visits ‘Not Benign’
Results of a preplanned subgroup analysis examining the risk for all-cause mortality after an LWBS visit were “particularly notable,” the authors wrote, with a 46% higher adjusted risk for death at 7 days and 24% higher adjusted risk at 30 days.
The observational study had several limitations, however. The authors could not draw conclusions regarding direct causes of the increased risk for severe short-term adverse health outcomes after an LWBS ED visit, and residual confounding is possible. Cause-of-death information was not available to generate hypotheses for future studies of potential causes. Furthermore, the findings may not be generalizable to systems without universal access to healthcare.
Nevertheless, the findings are a “concerning signal [and] should prompt interventions to address system- and population-level causes,” the authors wrote.
“Unfortunately, because of politics, since 2020, ED closures in Ontario have become more and more common and seem to be affecting more and more Ontarians,” said McNaughton. “It would be surprising if ED closure didn’t play some role in our findings.”
She added, “It is important to note that people in our study were relatively young, with a median age in their 40s; this makes our findings all the more concerning. Clinicians should be aware that LWBS ED visits are not necessarily benign, particularly when rates of LWBS ED visits are high.”
Unanswered Questions
The study raised the following questions that the authors are or will be investigating, according to McNaughton:
- Which patients are at greatest risk for bad outcomes if they leave the ED without being seen, and why?
- How much of the findings might be related to recent ED closures, longer ED wait times, or other factors? Are there geographic variations in risk?
- What can be done in the ED to prevent LWBS ED visits, and what can be changed outside the ED to prevent LWBS ED visits? For example, what can hospitals do to reduce boarding in the ED? If patients leave without being seen, should they be contacted to try to meet their health needs in other ways?
- What worked in terms of maintaining access to outpatient medical care, despite the considerable disruptions starting in 2020, and how can continued success be ensured?
To address the current situation, McNaughton said, “We need consistent, predictable, and sustained investment in our public healthcare system. We need long-term, consistent funding for primary care, ED care, as well as hospital and long-term care.”
“It takes years to recruit and train the teams of people necessary to provide the high-quality medical care that Canadians have a right to. There are no shortcuts,” she concluded.
‘Tragic Situation’
American College of Emergency Physicians (ACEP) spokesperson Jesse Pines, MD, chief of clinical innovation at US Acute Care Solutions; clinical professor of emergency medicine at George Washington University in Washington, DC; and professor of emergency medicine at Drexel University in Philadelphia, commented on the study for this news organization.
“Similar to what the authors found in their report, LWBS and other metrics — specifically boarding — have progressively increased in the United States, in particular, since the early part of 2021,” he said. “The primary factor in the US driving this, and one that ACEP is trying to address on a national scale, is the boarding of admitted patients.”
When the number of boarded patients increases, there is less space in the ED for new patients, and waits increase, Pines explained. Some patients leave without being seen, and a subset of those patients experience poor outcomes. “It’s a tragic situation that is worsening.”
“Emergency physicians like me always worry when patients leave without being seen,” he said. While some of those patients have self-limited conditions that will improve on their own, “some have critical life-threatening conditions that require care and hospitalization. The worry is that these patients experience poorer outcomes,” Pines said. “The authors showed that this is increasingly the case in Canada. The same is likely true in the US.”
The study was funded by the Canadian Institutes of Health Research. McNaughton and Pines declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Scientific Publications Face Credibility Crisis
The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.
Artificial Intelligence (AI) Spurs Low-Quality Submissions
According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.
Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.
This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.
Concerns Over Peer Reviews
The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.
She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.
AI Complicates Peer Review
The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.
Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.
In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”
The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’ remains a timeless recommendation that is likely to stay relevant for years to come.
This story was translated from Univadis Germany 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.
The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.
Artificial Intelligence (AI) Spurs Low-Quality Submissions
According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.
Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.
This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.
Concerns Over Peer Reviews
The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.
She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.
AI Complicates Peer Review
The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.
Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.
In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”
The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’ remains a timeless recommendation that is likely to stay relevant for years to come.
This story was translated from Univadis Germany 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.
The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.
Artificial Intelligence (AI) Spurs Low-Quality Submissions
According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.
Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.
This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.
Concerns Over Peer Reviews
The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.
She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.
AI Complicates Peer Review
The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.
Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.
In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”
The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’ remains a timeless recommendation that is likely to stay relevant for years to come.
This story was translated from Univadis Germany 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.
Implementation Research: Simple Text Reminders Help Increase Vaccine Uptake
This transcript has been edited for clarity.
I would like to briefly discuss a very interesting paper that appeared in Nature:“Megastudy Shows That Reminders Boost Vaccination but Adding Free Rides Does Not.”
Obviously, the paper has a provocative title. This is really an excellent example of what one might call implementation research, or quite frankly, what might work and what might not work in terms of having a very pragmatic goal. In this case, it was how do we get people to receive vaccinations.
This specific study looked at individuals who were scheduled to receive or were candidates to receive COVID-19 booster vaccinations. The question came up: If you gave them free rides to the location — this is obviously a high-risk population — would that increase the vaccination rate vs the other item that they were looking at here, which was potentially texting them to remind them?
The study very importantly and relevantly demonstrated, quite nicely, that offering free rides did not make a difference, but sending texts to remind them increased the 30-day vaccination rate in this population by 21%.
Again, it was a very pragmatic question that the trial addressed, and one might use this information in the future to increase the vaccination rate of a population where it is critical to do so. This type of research, which involves looking at very pragmatic questions and answering what is the optimal and most cost-effective way of doing it, should be encouraged.
I encourage you to look at this paper if you’re interested in this topic.
Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I would like to briefly discuss a very interesting paper that appeared in Nature:“Megastudy Shows That Reminders Boost Vaccination but Adding Free Rides Does Not.”
Obviously, the paper has a provocative title. This is really an excellent example of what one might call implementation research, or quite frankly, what might work and what might not work in terms of having a very pragmatic goal. In this case, it was how do we get people to receive vaccinations.
This specific study looked at individuals who were scheduled to receive or were candidates to receive COVID-19 booster vaccinations. The question came up: If you gave them free rides to the location — this is obviously a high-risk population — would that increase the vaccination rate vs the other item that they were looking at here, which was potentially texting them to remind them?
The study very importantly and relevantly demonstrated, quite nicely, that offering free rides did not make a difference, but sending texts to remind them increased the 30-day vaccination rate in this population by 21%.
Again, it was a very pragmatic question that the trial addressed, and one might use this information in the future to increase the vaccination rate of a population where it is critical to do so. This type of research, which involves looking at very pragmatic questions and answering what is the optimal and most cost-effective way of doing it, should be encouraged.
I encourage you to look at this paper if you’re interested in this topic.
Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I would like to briefly discuss a very interesting paper that appeared in Nature:“Megastudy Shows That Reminders Boost Vaccination but Adding Free Rides Does Not.”
Obviously, the paper has a provocative title. This is really an excellent example of what one might call implementation research, or quite frankly, what might work and what might not work in terms of having a very pragmatic goal. In this case, it was how do we get people to receive vaccinations.
This specific study looked at individuals who were scheduled to receive or were candidates to receive COVID-19 booster vaccinations. The question came up: If you gave them free rides to the location — this is obviously a high-risk population — would that increase the vaccination rate vs the other item that they were looking at here, which was potentially texting them to remind them?
The study very importantly and relevantly demonstrated, quite nicely, that offering free rides did not make a difference, but sending texts to remind them increased the 30-day vaccination rate in this population by 21%.
Again, it was a very pragmatic question that the trial addressed, and one might use this information in the future to increase the vaccination rate of a population where it is critical to do so. This type of research, which involves looking at very pragmatic questions and answering what is the optimal and most cost-effective way of doing it, should be encouraged.
I encourage you to look at this paper if you’re interested in this topic.
Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
Using AI to ID Osteoporosis: A Medico-Legal Minefield?
Could an artificial intelligence (AI)–driven tool that mines medical records for suspected cases of osteoporosis be so successful that it becomes a potential liability? Yes, according to Christopher White, PhD, executive director of Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research, and Enterprise, a research translation center in Liverpool, Australia.
In a thought-provoking presentation at the Endocrine Society’s AI in Healthcare Virtual Summit, White described the results after his fracture liaison team at Prince of Wales Hospital in Randwick, Australia, tried to plug the “osteoporosis treatment gap” by mining medical records to identify patients with the disorder.
‘Be Careful What You Wish For’
White and colleagues developed a robust standalone database over 20 years that informed fracture risk among patients with osteoporosis in Sydney. The database included all relevant clinical information, as well as bone density measurements, on about 30,000 patients and could be interrogated for randomized controlled trial recruitment.
However, a “crisis” occurred around 2011, when the team received a recruitment request for the first head-to-head comparison of alendronate with romosozumab. “We had numerous postmenopausal women in the age range with the required bone density, but we hadn’t captured the severity of their vertebral fracture or how many they actually had,” White told the this news organization. For recruitment into the study, participants must have had at least two moderate or severe vertebral fractures or a proximal vertebral fracture that was sustained between 3 and 24 months before recruitment.
White turned to his hospital’s mainframe, which had coding data and time intervals for patients who were admitted with vertebral or hip fractures. He calculated how many patients who met the study criteria had been discharged and how many of those he thought he’d be able to capture through the mainframe. He was confident he would have enough, but he was wrong. He underrecruited and could not participate in the trial.
Determined not to wind up in a similar situation in the future, he investigated and found that other centers were struggling with similar problems. This led to a collaboration with four investigators who were using AI and Advanced Encryption Standard (AES) coding to identify patients at risk for osteoporotic fractures. White, meanwhile, had developed a natural language processing tool called XRAIT that also identified patients at fracture risk. A study comparing the two electronic search programs, which screen medical records for fractures, found that both reliably identified patients who had had a fracture. White and his colleagues concluded that hybrid tools combining XRAIT and AES would likely improve the identification of patients with osteoporosis who would require follow-up or might participate in future trials.
Those patients were not being identified sooner for multiple reasons, White explained. Sometimes, the radiologist would report osteoporosis, but it wouldn’t get coded. Or, in the emergency department, a patient with a fracture would be treated and then sent home, and the possibility of osteoporosis wasn’t reported.
“As we went deeper and deeper with our tools into the medical record, we found more and more patients who hadn’t been coded or reported but who actually had osteoporosis,” White said. “It was incredibly prevalent.”
But the number of patients identified was more than the hospital could comfortably handle.
Ironically, he added, “To my relief and probably not to the benefit of the patients, there was a system upgrade of the radiology reporting system, which was incompatible with the natural language processing technology that I had installed. The AI was turned off at that point, but I had a look over the edge and into the mine pit.”
“The lesson learned,” White told this news organization, is “If you mine the medical record for unidentified patients before you know what to do with the output, you create a medico-legal minefield. You need to be careful what you wish for with technology, because it may actually come true.”
Grappling With the Treatment Gap
An (over)abundance of patients is likely contributing to the “osteoporosis treatment gap” that Australia’s fracture liaison services, which handle many of these patients, are grappling with. One recent meta-analysis showed that not all eligible patients are treated and that not all patients who are treated actually start treatment. Another study showed that only a minority of patients — anywhere between 20% and 40% — who start are still persisting at about 3 years, White said.
Various types of fracture liaison services exist, he noted. The model that has been shown to best promote adherence is the one requiring clinicians to “identify, educate [usually, the primary care physician], evaluate, start treatment, continue treatment, and follow-up at 12 months for to confirm that there is adherence.”
What’s happening now, he said, is that the technology is identifying a high number of vertebral crush fractures, and there’s no education or evaluation. “The radiologist just refers the patient to a primary care physician and hopes for the best. AI isn’t contributing to solving the treatment gap problem; it’s amplifying it. It’s ahead of the ability of organizations to accommodate the findings.”
Solutions, he said, would require support at the top of health systems and organizations, and funding to proceed; data surveys concentrating on vertical integration of the medical record to follow patients wherever they are — eg, hospital, primary care — in their health journeys; a workflow with synchronous diagnosis and treatment planning, delivery, monitoring, and payment; and clinical and community champions advocating and “leading the charge in health tech.”
Furthermore, he advised, organizations need to be “very, very careful with safety and security — that is, managing the digital risks.”
“Oscar Wilde said there are two tragedies in life: One is not getting what one wants, and the other is getting it,” White concluded. “In my career, we’ve moved on from not knowing how to treat osteoporosis to knowing how to treat it. And that is both an asset and a liability.”
A version of this article first appeared on Medscape.com.
Could an artificial intelligence (AI)–driven tool that mines medical records for suspected cases of osteoporosis be so successful that it becomes a potential liability? Yes, according to Christopher White, PhD, executive director of Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research, and Enterprise, a research translation center in Liverpool, Australia.
In a thought-provoking presentation at the Endocrine Society’s AI in Healthcare Virtual Summit, White described the results after his fracture liaison team at Prince of Wales Hospital in Randwick, Australia, tried to plug the “osteoporosis treatment gap” by mining medical records to identify patients with the disorder.
‘Be Careful What You Wish For’
White and colleagues developed a robust standalone database over 20 years that informed fracture risk among patients with osteoporosis in Sydney. The database included all relevant clinical information, as well as bone density measurements, on about 30,000 patients and could be interrogated for randomized controlled trial recruitment.
However, a “crisis” occurred around 2011, when the team received a recruitment request for the first head-to-head comparison of alendronate with romosozumab. “We had numerous postmenopausal women in the age range with the required bone density, but we hadn’t captured the severity of their vertebral fracture or how many they actually had,” White told the this news organization. For recruitment into the study, participants must have had at least two moderate or severe vertebral fractures or a proximal vertebral fracture that was sustained between 3 and 24 months before recruitment.
White turned to his hospital’s mainframe, which had coding data and time intervals for patients who were admitted with vertebral or hip fractures. He calculated how many patients who met the study criteria had been discharged and how many of those he thought he’d be able to capture through the mainframe. He was confident he would have enough, but he was wrong. He underrecruited and could not participate in the trial.
Determined not to wind up in a similar situation in the future, he investigated and found that other centers were struggling with similar problems. This led to a collaboration with four investigators who were using AI and Advanced Encryption Standard (AES) coding to identify patients at risk for osteoporotic fractures. White, meanwhile, had developed a natural language processing tool called XRAIT that also identified patients at fracture risk. A study comparing the two electronic search programs, which screen medical records for fractures, found that both reliably identified patients who had had a fracture. White and his colleagues concluded that hybrid tools combining XRAIT and AES would likely improve the identification of patients with osteoporosis who would require follow-up or might participate in future trials.
Those patients were not being identified sooner for multiple reasons, White explained. Sometimes, the radiologist would report osteoporosis, but it wouldn’t get coded. Or, in the emergency department, a patient with a fracture would be treated and then sent home, and the possibility of osteoporosis wasn’t reported.
“As we went deeper and deeper with our tools into the medical record, we found more and more patients who hadn’t been coded or reported but who actually had osteoporosis,” White said. “It was incredibly prevalent.”
But the number of patients identified was more than the hospital could comfortably handle.
Ironically, he added, “To my relief and probably not to the benefit of the patients, there was a system upgrade of the radiology reporting system, which was incompatible with the natural language processing technology that I had installed. The AI was turned off at that point, but I had a look over the edge and into the mine pit.”
“The lesson learned,” White told this news organization, is “If you mine the medical record for unidentified patients before you know what to do with the output, you create a medico-legal minefield. You need to be careful what you wish for with technology, because it may actually come true.”
Grappling With the Treatment Gap
An (over)abundance of patients is likely contributing to the “osteoporosis treatment gap” that Australia’s fracture liaison services, which handle many of these patients, are grappling with. One recent meta-analysis showed that not all eligible patients are treated and that not all patients who are treated actually start treatment. Another study showed that only a minority of patients — anywhere between 20% and 40% — who start are still persisting at about 3 years, White said.
Various types of fracture liaison services exist, he noted. The model that has been shown to best promote adherence is the one requiring clinicians to “identify, educate [usually, the primary care physician], evaluate, start treatment, continue treatment, and follow-up at 12 months for to confirm that there is adherence.”
What’s happening now, he said, is that the technology is identifying a high number of vertebral crush fractures, and there’s no education or evaluation. “The radiologist just refers the patient to a primary care physician and hopes for the best. AI isn’t contributing to solving the treatment gap problem; it’s amplifying it. It’s ahead of the ability of organizations to accommodate the findings.”
Solutions, he said, would require support at the top of health systems and organizations, and funding to proceed; data surveys concentrating on vertical integration of the medical record to follow patients wherever they are — eg, hospital, primary care — in their health journeys; a workflow with synchronous diagnosis and treatment planning, delivery, monitoring, and payment; and clinical and community champions advocating and “leading the charge in health tech.”
Furthermore, he advised, organizations need to be “very, very careful with safety and security — that is, managing the digital risks.”
“Oscar Wilde said there are two tragedies in life: One is not getting what one wants, and the other is getting it,” White concluded. “In my career, we’ve moved on from not knowing how to treat osteoporosis to knowing how to treat it. And that is both an asset and a liability.”
A version of this article first appeared on Medscape.com.
Could an artificial intelligence (AI)–driven tool that mines medical records for suspected cases of osteoporosis be so successful that it becomes a potential liability? Yes, according to Christopher White, PhD, executive director of Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research, and Enterprise, a research translation center in Liverpool, Australia.
In a thought-provoking presentation at the Endocrine Society’s AI in Healthcare Virtual Summit, White described the results after his fracture liaison team at Prince of Wales Hospital in Randwick, Australia, tried to plug the “osteoporosis treatment gap” by mining medical records to identify patients with the disorder.
‘Be Careful What You Wish For’
White and colleagues developed a robust standalone database over 20 years that informed fracture risk among patients with osteoporosis in Sydney. The database included all relevant clinical information, as well as bone density measurements, on about 30,000 patients and could be interrogated for randomized controlled trial recruitment.
However, a “crisis” occurred around 2011, when the team received a recruitment request for the first head-to-head comparison of alendronate with romosozumab. “We had numerous postmenopausal women in the age range with the required bone density, but we hadn’t captured the severity of their vertebral fracture or how many they actually had,” White told the this news organization. For recruitment into the study, participants must have had at least two moderate or severe vertebral fractures or a proximal vertebral fracture that was sustained between 3 and 24 months before recruitment.
White turned to his hospital’s mainframe, which had coding data and time intervals for patients who were admitted with vertebral or hip fractures. He calculated how many patients who met the study criteria had been discharged and how many of those he thought he’d be able to capture through the mainframe. He was confident he would have enough, but he was wrong. He underrecruited and could not participate in the trial.
Determined not to wind up in a similar situation in the future, he investigated and found that other centers were struggling with similar problems. This led to a collaboration with four investigators who were using AI and Advanced Encryption Standard (AES) coding to identify patients at risk for osteoporotic fractures. White, meanwhile, had developed a natural language processing tool called XRAIT that also identified patients at fracture risk. A study comparing the two electronic search programs, which screen medical records for fractures, found that both reliably identified patients who had had a fracture. White and his colleagues concluded that hybrid tools combining XRAIT and AES would likely improve the identification of patients with osteoporosis who would require follow-up or might participate in future trials.
Those patients were not being identified sooner for multiple reasons, White explained. Sometimes, the radiologist would report osteoporosis, but it wouldn’t get coded. Or, in the emergency department, a patient with a fracture would be treated and then sent home, and the possibility of osteoporosis wasn’t reported.
“As we went deeper and deeper with our tools into the medical record, we found more and more patients who hadn’t been coded or reported but who actually had osteoporosis,” White said. “It was incredibly prevalent.”
But the number of patients identified was more than the hospital could comfortably handle.
Ironically, he added, “To my relief and probably not to the benefit of the patients, there was a system upgrade of the radiology reporting system, which was incompatible with the natural language processing technology that I had installed. The AI was turned off at that point, but I had a look over the edge and into the mine pit.”
“The lesson learned,” White told this news organization, is “If you mine the medical record for unidentified patients before you know what to do with the output, you create a medico-legal minefield. You need to be careful what you wish for with technology, because it may actually come true.”
Grappling With the Treatment Gap
An (over)abundance of patients is likely contributing to the “osteoporosis treatment gap” that Australia’s fracture liaison services, which handle many of these patients, are grappling with. One recent meta-analysis showed that not all eligible patients are treated and that not all patients who are treated actually start treatment. Another study showed that only a minority of patients — anywhere between 20% and 40% — who start are still persisting at about 3 years, White said.
Various types of fracture liaison services exist, he noted. The model that has been shown to best promote adherence is the one requiring clinicians to “identify, educate [usually, the primary care physician], evaluate, start treatment, continue treatment, and follow-up at 12 months for to confirm that there is adherence.”
What’s happening now, he said, is that the technology is identifying a high number of vertebral crush fractures, and there’s no education or evaluation. “The radiologist just refers the patient to a primary care physician and hopes for the best. AI isn’t contributing to solving the treatment gap problem; it’s amplifying it. It’s ahead of the ability of organizations to accommodate the findings.”
Solutions, he said, would require support at the top of health systems and organizations, and funding to proceed; data surveys concentrating on vertical integration of the medical record to follow patients wherever they are — eg, hospital, primary care — in their health journeys; a workflow with synchronous diagnosis and treatment planning, delivery, monitoring, and payment; and clinical and community champions advocating and “leading the charge in health tech.”
Furthermore, he advised, organizations need to be “very, very careful with safety and security — that is, managing the digital risks.”
“Oscar Wilde said there are two tragedies in life: One is not getting what one wants, and the other is getting it,” White concluded. “In my career, we’ve moved on from not knowing how to treat osteoporosis to knowing how to treat it. And that is both an asset and a liability.”
A version of this article first appeared on Medscape.com.
Simufilam: Just Another Placebo
An Alzheimer’s drug trial failing is, unfortunately, nothing new. This one, however, had more baggage behind it than most.
Like all of these things, it was worth a try. It’s an interesting molecule with a reasonable mechanism of action.
But the trials have been raising questions for a few years, with allegations of misconduct against the drug’s co-discoverer Hoau-Yan Wang. He’s been indicted for defrauding the National Institutes of Health of $16 million in grants related to the drug. There have been concerns over doctored images and other not-so-minor issues in trying to move simufilam forward. Cassava itself agreed to pay the Securities and Exchange Commission $40 million in 2024 to settle charges about misleading investors.
Yet, like an innocent child with criminal parents, many of us hoped that the drug would work, regardless of the ethical shenanigans behind it. On the front lines we deal with a tragic disease that robs people of what makes them human and robs the families who have to live with it.
As the wheels started to come off the bus I told a friend, “it would be really sad if this drug is THE ONE and it never gets to finish trials because of everything else.”
Now we know it isn’t. Regardless of the controversy, the final data show that simufilam is just another placebo, joining the ranks of many others in the Alzheimer’s development graveyard.
Yes, there is a vague sense of jubilation behind it. I believe in fair play, and it’s good to know that those who misled investors and falsified data were wrong and will never have their day in the sun.
At the same time, however, I’m disappointed. I’m happy that the drug at least got a chance to prove itself, but when it’s all said and done, it doesn’t do anything.
I feel bad for the innocent people in the company, who had nothing to do with the scheming and were just hoping the drug would go somewhere. The majority, if not all, of them will likely lose their jobs. Like me, they have families, bills, and mortgages.
But I’m even more disappointed for the patients and families who only wanted an effective treatment for Alzheimer’s disease, and were hoping that, regardless of its dirty laundry, simufilam would work.
They’re the ones that I, and many other neurologists, have to face every day when they ask “is there anything new out?” and we sadly shake our heads.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
An Alzheimer’s drug trial failing is, unfortunately, nothing new. This one, however, had more baggage behind it than most.
Like all of these things, it was worth a try. It’s an interesting molecule with a reasonable mechanism of action.
But the trials have been raising questions for a few years, with allegations of misconduct against the drug’s co-discoverer Hoau-Yan Wang. He’s been indicted for defrauding the National Institutes of Health of $16 million in grants related to the drug. There have been concerns over doctored images and other not-so-minor issues in trying to move simufilam forward. Cassava itself agreed to pay the Securities and Exchange Commission $40 million in 2024 to settle charges about misleading investors.
Yet, like an innocent child with criminal parents, many of us hoped that the drug would work, regardless of the ethical shenanigans behind it. On the front lines we deal with a tragic disease that robs people of what makes them human and robs the families who have to live with it.
As the wheels started to come off the bus I told a friend, “it would be really sad if this drug is THE ONE and it never gets to finish trials because of everything else.”
Now we know it isn’t. Regardless of the controversy, the final data show that simufilam is just another placebo, joining the ranks of many others in the Alzheimer’s development graveyard.
Yes, there is a vague sense of jubilation behind it. I believe in fair play, and it’s good to know that those who misled investors and falsified data were wrong and will never have their day in the sun.
At the same time, however, I’m disappointed. I’m happy that the drug at least got a chance to prove itself, but when it’s all said and done, it doesn’t do anything.
I feel bad for the innocent people in the company, who had nothing to do with the scheming and were just hoping the drug would go somewhere. The majority, if not all, of them will likely lose their jobs. Like me, they have families, bills, and mortgages.
But I’m even more disappointed for the patients and families who only wanted an effective treatment for Alzheimer’s disease, and were hoping that, regardless of its dirty laundry, simufilam would work.
They’re the ones that I, and many other neurologists, have to face every day when they ask “is there anything new out?” and we sadly shake our heads.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
An Alzheimer’s drug trial failing is, unfortunately, nothing new. This one, however, had more baggage behind it than most.
Like all of these things, it was worth a try. It’s an interesting molecule with a reasonable mechanism of action.
But the trials have been raising questions for a few years, with allegations of misconduct against the drug’s co-discoverer Hoau-Yan Wang. He’s been indicted for defrauding the National Institutes of Health of $16 million in grants related to the drug. There have been concerns over doctored images and other not-so-minor issues in trying to move simufilam forward. Cassava itself agreed to pay the Securities and Exchange Commission $40 million in 2024 to settle charges about misleading investors.
Yet, like an innocent child with criminal parents, many of us hoped that the drug would work, regardless of the ethical shenanigans behind it. On the front lines we deal with a tragic disease that robs people of what makes them human and robs the families who have to live with it.
As the wheels started to come off the bus I told a friend, “it would be really sad if this drug is THE ONE and it never gets to finish trials because of everything else.”
Now we know it isn’t. Regardless of the controversy, the final data show that simufilam is just another placebo, joining the ranks of many others in the Alzheimer’s development graveyard.
Yes, there is a vague sense of jubilation behind it. I believe in fair play, and it’s good to know that those who misled investors and falsified data were wrong and will never have their day in the sun.
At the same time, however, I’m disappointed. I’m happy that the drug at least got a chance to prove itself, but when it’s all said and done, it doesn’t do anything.
I feel bad for the innocent people in the company, who had nothing to do with the scheming and were just hoping the drug would go somewhere. The majority, if not all, of them will likely lose their jobs. Like me, they have families, bills, and mortgages.
But I’m even more disappointed for the patients and families who only wanted an effective treatment for Alzheimer’s disease, and were hoping that, regardless of its dirty laundry, simufilam would work.
They’re the ones that I, and many other neurologists, have to face every day when they ask “is there anything new out?” and we sadly shake our heads.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Cellular Therapies for Solid Tumors: The Next Big Thing?
The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.
First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue.
“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”
As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs).
“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.
‘Reverse Engineering’
In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy.
Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.
“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer?
Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand.
“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”
In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.
Cell Therapies Include CAR T Cells and TCRT
In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.
In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).
In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner.
“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.
TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies.
Decades in the Making
The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.
Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics.
“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.”
Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.
“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.
In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas.
The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.
Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”
Risk-Benefit Profiles Depend on Mechanism of Action
If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor.
“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.
A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.
“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”
A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner.
In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes.
“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”
Promise of PRAME
Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study.
“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”
Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).
The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.
Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile.
Accelerated Approvals, Boxed Warnings
The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT.
Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.
With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.
The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses.
The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).
In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel.
The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.
New Hope for Patients
Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.
“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”
For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.
“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.
Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.
A version of this article appeared on Medscape.com.
The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.
First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue.
“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”
As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs).
“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.
‘Reverse Engineering’
In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy.
Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.
“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer?
Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand.
“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”
In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.
Cell Therapies Include CAR T Cells and TCRT
In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.
In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).
In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner.
“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.
TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies.
Decades in the Making
The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.
Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics.
“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.”
Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.
“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.
In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas.
The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.
Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”
Risk-Benefit Profiles Depend on Mechanism of Action
If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor.
“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.
A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.
“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”
A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner.
In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes.
“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”
Promise of PRAME
Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study.
“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”
Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).
The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.
Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile.
Accelerated Approvals, Boxed Warnings
The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT.
Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.
With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.
The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses.
The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).
In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel.
The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.
New Hope for Patients
Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.
“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”
For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.
“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.
Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.
A version of this article appeared on Medscape.com.
The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.
First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue.
“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”
As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs).
“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.
‘Reverse Engineering’
In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy.
Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.
“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer?
Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand.
“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”
In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.
Cell Therapies Include CAR T Cells and TCRT
In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.
In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).
In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner.
“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.
TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies.
Decades in the Making
The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.
Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics.
“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.”
Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.
“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.
In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas.
The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.
Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”
Risk-Benefit Profiles Depend on Mechanism of Action
If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor.
“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.
A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.
“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”
A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner.
In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes.
“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”
Promise of PRAME
Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study.
“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”
Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).
The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.
Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile.
Accelerated Approvals, Boxed Warnings
The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT.
Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.
With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.
The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses.
The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).
In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel.
The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.
New Hope for Patients
Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.
“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”
For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.
“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.
Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.
A version of this article appeared on Medscape.com.
Medical Education and Firearm-Related Deaths
For the third straight year, firearms killed more children and teens than any other cause, including motor vehicle crashes and cancer. The population-wide toll taken by guns is equally as discouraging. Finally, this elephant in the room is getting some attention from the medical community, but the voices asking for change have most recently been coming from medical students who feel that gun violence deserves to be given a larger role in their education. It’s unclear why this plea is coming from the younger end of the medical community. It may be that, unlike most of their older instructors, these 18- to 25-year-olds have grown up under the growing threat of school shootings and become uncomfortably accustomed to active shooter drills.
Should We Look to Medical School for Answers?
But, does the medical community need to take gun violence more seriously than the rest of the population? What should our response look like? To answer those questions we need to take several steps back to view the bigger picture.
Is the medical community more responsible for this current situation than any other segment of the population? Do physicians bear any more culpability than publishers who sell gun-related magazines? Since its inception pediatrics has taken on the role of advocate for children and their health and well-being. But, is there more we can and should do other than turn up the volume on our advocacy?
While still taking the longer view, let’s ask ourselves what the role of medical school should be. Not just with respect to gun violence but in producing physicians and healthcare providers. We are approaching a crisis in primary care as it loses appeal with physicians at both ends of the age continuum. It could be because it pays poorly — certainly in relation to the cost of medical school — or because the awareness that if done well primary care requires a commitment that is difficult to square with many individuals’ lifestyle expectations.
Is the traditional medical school the right place to be training primary care providers? Medical school is currently aimed at broad and deep exposure. The student will be exposed to the all the diseases to which he or she might be seeing anywhere in the world and at the same time will have learned the mechanisms down to the cellular level that lies behind that pathology. Does a primary care pediatrician practicing in a small city or suburbia need that depth of training? He or she might benefit from some breadth. But maybe it should be focused on socioeconomic and geographic population the doctor is likely to see. This is particularly true for gun-related deaths.
Returning our attention to gun violence and its relation to healthcare, let’s ask ourselves what role the traditional medical school should play. Should it be a breeding ground for gun control advocates? When physicians speak people tend to listen but our effectiveness on issues such as immunizations and gun control has not been what many have hoped for. The supply of guns available to the public in this country is staggering and certainly contributes to gun-related injuries and death. However, I’m afraid that making a significant dent in that supply, given our political history and current climate, is an issue whose ship has sailed.
On the other hand, as gun advocates are often quoted as saying, “it’s not guns that kill, it’s people.” We don’t need to go into to the fallacy of this argument, but it gives us a starting point from which a medical school might focus its efforts on addressing the fallout from gun violence. A curriculum that begins with a presentation of the grizzly statistics and moves on to research about gun-related mental health issues and the social environments that breed violence makes good sense. Recanting the depressing history of how our society got to this place, in which guns outnumber people, should be part of the undergraduate curriculum.
Addressing the specifics of gun safety and suicide prevention in general with families and individuals would be more appropriate during clinical specialty training.
How big a chunk of the curriculum should be committed to gun violence and its fallout? Some of the call for change seems to be suggesting a semester-long course. However, we must accept the reality that instructional time in medical school is a finite asset. Although gunshots are the leading cause of death in children, how effective will even the most cleverly crafted curriculum be in moving the needle on the embarrassing data?
Given what is known about the problem, a day, or at most a week would be sufficient in class time. This could include personal presentations by victims or family members. I’m sure there are some who would see that as insufficient. But I see it as realistic. For the large urban schools, observing an evening shift in the trauma unit of an ER could be a potent addition.
Beyond this, a commitment by the school to host seminars and workshops devoted to gun violence could be an important component. It might also be helpful for a school or training program to promote the habit of whenever an instructor is introducing a potentially fatal disease to the students for the first time, he or she would begin with “To put this in perspective, you should remember that xxx thousand children die of gunshot wounds every year.”
Unfortunately, like obesity, gun-related deaths and injuries are the result of our society’s failure to muster the political will to act in our best interest as a nation. The medical community is left to clean up the collateral damage. There is always more that we could do, but we must be thoughtful in how we invest our energies in the effort.
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.
For the third straight year, firearms killed more children and teens than any other cause, including motor vehicle crashes and cancer. The population-wide toll taken by guns is equally as discouraging. Finally, this elephant in the room is getting some attention from the medical community, but the voices asking for change have most recently been coming from medical students who feel that gun violence deserves to be given a larger role in their education. It’s unclear why this plea is coming from the younger end of the medical community. It may be that, unlike most of their older instructors, these 18- to 25-year-olds have grown up under the growing threat of school shootings and become uncomfortably accustomed to active shooter drills.
Should We Look to Medical School for Answers?
But, does the medical community need to take gun violence more seriously than the rest of the population? What should our response look like? To answer those questions we need to take several steps back to view the bigger picture.
Is the medical community more responsible for this current situation than any other segment of the population? Do physicians bear any more culpability than publishers who sell gun-related magazines? Since its inception pediatrics has taken on the role of advocate for children and their health and well-being. But, is there more we can and should do other than turn up the volume on our advocacy?
While still taking the longer view, let’s ask ourselves what the role of medical school should be. Not just with respect to gun violence but in producing physicians and healthcare providers. We are approaching a crisis in primary care as it loses appeal with physicians at both ends of the age continuum. It could be because it pays poorly — certainly in relation to the cost of medical school — or because the awareness that if done well primary care requires a commitment that is difficult to square with many individuals’ lifestyle expectations.
Is the traditional medical school the right place to be training primary care providers? Medical school is currently aimed at broad and deep exposure. The student will be exposed to the all the diseases to which he or she might be seeing anywhere in the world and at the same time will have learned the mechanisms down to the cellular level that lies behind that pathology. Does a primary care pediatrician practicing in a small city or suburbia need that depth of training? He or she might benefit from some breadth. But maybe it should be focused on socioeconomic and geographic population the doctor is likely to see. This is particularly true for gun-related deaths.
Returning our attention to gun violence and its relation to healthcare, let’s ask ourselves what role the traditional medical school should play. Should it be a breeding ground for gun control advocates? When physicians speak people tend to listen but our effectiveness on issues such as immunizations and gun control has not been what many have hoped for. The supply of guns available to the public in this country is staggering and certainly contributes to gun-related injuries and death. However, I’m afraid that making a significant dent in that supply, given our political history and current climate, is an issue whose ship has sailed.
On the other hand, as gun advocates are often quoted as saying, “it’s not guns that kill, it’s people.” We don’t need to go into to the fallacy of this argument, but it gives us a starting point from which a medical school might focus its efforts on addressing the fallout from gun violence. A curriculum that begins with a presentation of the grizzly statistics and moves on to research about gun-related mental health issues and the social environments that breed violence makes good sense. Recanting the depressing history of how our society got to this place, in which guns outnumber people, should be part of the undergraduate curriculum.
Addressing the specifics of gun safety and suicide prevention in general with families and individuals would be more appropriate during clinical specialty training.
How big a chunk of the curriculum should be committed to gun violence and its fallout? Some of the call for change seems to be suggesting a semester-long course. However, we must accept the reality that instructional time in medical school is a finite asset. Although gunshots are the leading cause of death in children, how effective will even the most cleverly crafted curriculum be in moving the needle on the embarrassing data?
Given what is known about the problem, a day, or at most a week would be sufficient in class time. This could include personal presentations by victims or family members. I’m sure there are some who would see that as insufficient. But I see it as realistic. For the large urban schools, observing an evening shift in the trauma unit of an ER could be a potent addition.
Beyond this, a commitment by the school to host seminars and workshops devoted to gun violence could be an important component. It might also be helpful for a school or training program to promote the habit of whenever an instructor is introducing a potentially fatal disease to the students for the first time, he or she would begin with “To put this in perspective, you should remember that xxx thousand children die of gunshot wounds every year.”
Unfortunately, like obesity, gun-related deaths and injuries are the result of our society’s failure to muster the political will to act in our best interest as a nation. The medical community is left to clean up the collateral damage. There is always more that we could do, but we must be thoughtful in how we invest our energies in the effort.
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.
For the third straight year, firearms killed more children and teens than any other cause, including motor vehicle crashes and cancer. The population-wide toll taken by guns is equally as discouraging. Finally, this elephant in the room is getting some attention from the medical community, but the voices asking for change have most recently been coming from medical students who feel that gun violence deserves to be given a larger role in their education. It’s unclear why this plea is coming from the younger end of the medical community. It may be that, unlike most of their older instructors, these 18- to 25-year-olds have grown up under the growing threat of school shootings and become uncomfortably accustomed to active shooter drills.
Should We Look to Medical School for Answers?
But, does the medical community need to take gun violence more seriously than the rest of the population? What should our response look like? To answer those questions we need to take several steps back to view the bigger picture.
Is the medical community more responsible for this current situation than any other segment of the population? Do physicians bear any more culpability than publishers who sell gun-related magazines? Since its inception pediatrics has taken on the role of advocate for children and their health and well-being. But, is there more we can and should do other than turn up the volume on our advocacy?
While still taking the longer view, let’s ask ourselves what the role of medical school should be. Not just with respect to gun violence but in producing physicians and healthcare providers. We are approaching a crisis in primary care as it loses appeal with physicians at both ends of the age continuum. It could be because it pays poorly — certainly in relation to the cost of medical school — or because the awareness that if done well primary care requires a commitment that is difficult to square with many individuals’ lifestyle expectations.
Is the traditional medical school the right place to be training primary care providers? Medical school is currently aimed at broad and deep exposure. The student will be exposed to the all the diseases to which he or she might be seeing anywhere in the world and at the same time will have learned the mechanisms down to the cellular level that lies behind that pathology. Does a primary care pediatrician practicing in a small city or suburbia need that depth of training? He or she might benefit from some breadth. But maybe it should be focused on socioeconomic and geographic population the doctor is likely to see. This is particularly true for gun-related deaths.
Returning our attention to gun violence and its relation to healthcare, let’s ask ourselves what role the traditional medical school should play. Should it be a breeding ground for gun control advocates? When physicians speak people tend to listen but our effectiveness on issues such as immunizations and gun control has not been what many have hoped for. The supply of guns available to the public in this country is staggering and certainly contributes to gun-related injuries and death. However, I’m afraid that making a significant dent in that supply, given our political history and current climate, is an issue whose ship has sailed.
On the other hand, as gun advocates are often quoted as saying, “it’s not guns that kill, it’s people.” We don’t need to go into to the fallacy of this argument, but it gives us a starting point from which a medical school might focus its efforts on addressing the fallout from gun violence. A curriculum that begins with a presentation of the grizzly statistics and moves on to research about gun-related mental health issues and the social environments that breed violence makes good sense. Recanting the depressing history of how our society got to this place, in which guns outnumber people, should be part of the undergraduate curriculum.
Addressing the specifics of gun safety and suicide prevention in general with families and individuals would be more appropriate during clinical specialty training.
How big a chunk of the curriculum should be committed to gun violence and its fallout? Some of the call for change seems to be suggesting a semester-long course. However, we must accept the reality that instructional time in medical school is a finite asset. Although gunshots are the leading cause of death in children, how effective will even the most cleverly crafted curriculum be in moving the needle on the embarrassing data?
Given what is known about the problem, a day, or at most a week would be sufficient in class time. This could include personal presentations by victims or family members. I’m sure there are some who would see that as insufficient. But I see it as realistic. For the large urban schools, observing an evening shift in the trauma unit of an ER could be a potent addition.
Beyond this, a commitment by the school to host seminars and workshops devoted to gun violence could be an important component. It might also be helpful for a school or training program to promote the habit of whenever an instructor is introducing a potentially fatal disease to the students for the first time, he or she would begin with “To put this in perspective, you should remember that xxx thousand children die of gunshot wounds every year.”
Unfortunately, like obesity, gun-related deaths and injuries are the result of our society’s failure to muster the political will to act in our best interest as a nation. The medical community is left to clean up the collateral damage. There is always more that we could do, but we must be thoughtful in how we invest our energies in the effort.
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.
A Cancer Patient’s Bittersweet Reminder
Recently, a 40-year-old woman took to Facebook to announce that she had died.
Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”
I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.
She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.
I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.
I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.
I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)
Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.
In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.
Thank you, Ms. Davies, for the reminder.
Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.
Recently, a 40-year-old woman took to Facebook to announce that she had died.
Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”
I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.
She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.
I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.
I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.
I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)
Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.
In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.
Thank you, Ms. Davies, for the reminder.
Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.
Recently, a 40-year-old woman took to Facebook to announce that she had died.
Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”
I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.
She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.
I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.
I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.
I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)
Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.
In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.
Thank you, Ms. Davies, for the reminder.
Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.
70% of US Counties Have No Endocrinologist, New Study Finds
according to a new analysis by GoodRx, a company that provides discount coupons for medications.
A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis.
The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.
GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.
Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.
The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.
In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.
Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.
Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.
To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.
Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.
The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.
GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”
Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.
Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.
Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.
The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.
The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.
It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.
“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”
A version of this article appeared on Medscape.com.
according to a new analysis by GoodRx, a company that provides discount coupons for medications.
A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis.
The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.
GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.
Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.
The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.
In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.
Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.
Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.
To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.
Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.
The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.
GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”
Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.
Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.
Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.
The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.
The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.
It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.
“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”
A version of this article appeared on Medscape.com.
according to a new analysis by GoodRx, a company that provides discount coupons for medications.
A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis.
The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.
GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.
Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.
The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.
In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.
Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.
Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.
To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.
Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.
The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.
GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”
Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.
Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.
Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.
The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.
The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.
It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.
“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”
A version of this article appeared on Medscape.com.
Reality of Night Shifts: How to Stay Sharp and Healthy
Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.
“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”
For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.
While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.
Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers who sleep 6 or fewer hours a night have at least one sleep disorder.
Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents.
Residency programs recently have been experimenting with shorter call schedules.
Catching Zzs
Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.
“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”
deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”
Blackout curtains may have helped, she added.
“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”
As a chief resident, she chooses never to sleep during night shifts.
“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”
But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.
Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.
When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.
“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.
To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.
Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.
Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.
Bypass Vending Machines
Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.
“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”
Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”
She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.
To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.
Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.
Take the Stairs
Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”
Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”
Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.
Ask for a Ride
Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”
The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”
Promoting Mental Health
The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.
“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”
“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.
She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”
For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.
A version of this article first appeared on Medscape.com.
Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.
“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”
For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.
While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.
Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers who sleep 6 or fewer hours a night have at least one sleep disorder.
Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents.
Residency programs recently have been experimenting with shorter call schedules.
Catching Zzs
Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.
“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”
deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”
Blackout curtains may have helped, she added.
“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”
As a chief resident, she chooses never to sleep during night shifts.
“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”
But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.
Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.
When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.
“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.
To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.
Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.
Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.
Bypass Vending Machines
Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.
“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”
Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”
She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.
To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.
Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.
Take the Stairs
Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”
Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”
Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.
Ask for a Ride
Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”
The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”
Promoting Mental Health
The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.
“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”
“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.
She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”
For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.
A version of this article first appeared on Medscape.com.
Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.
“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”
For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.
While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.
Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers who sleep 6 or fewer hours a night have at least one sleep disorder.
Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents.
Residency programs recently have been experimenting with shorter call schedules.
Catching Zzs
Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.
“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”
deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”
Blackout curtains may have helped, she added.
“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”
As a chief resident, she chooses never to sleep during night shifts.
“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”
But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.
Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.
When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.
“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.
To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.
Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.
Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.
Bypass Vending Machines
Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.
“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”
Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”
She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.
To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.
Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.
Take the Stairs
Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”
Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”
Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.
Ask for a Ride
Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”
The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”
Promoting Mental Health
The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.
“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”
“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.
She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”
For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.
A version of this article first appeared on Medscape.com.