Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

There have been increases in suspected suicidal cannabis exposures reported to U.S. poison control centers over the past 13 years. The increases were notable both during and after the pandemic and were highest among children and female persons.

Investigators examined closed cases of cannabis-related human exposures that were coded as intentional-suspected suicidal.

Of note, there was a statistically significant increase in cannabis poisonings in young children (5-13 years) in 2021, during the pandemic, compared with 2019, a prepandemic year (3.1% vs. 1.3%; P < .001), the researchers report.

“This may speak to both increased access to cannabis as well as poor mental health status during the pandemic period,” study investigator Tracy Klein, PhD, assistant director, Center for Cannabis Policy, Research and Outreach, Washington State University Vancouver, Mount Vista, said in an interview.

The study was published online  in JAMA Network Open.

Reports of intentional poisonings with cannabis increased by roughly 17% annually over the study period. Most cases occurred in recent years and involved individuals aged 14-64 years. Nearly all (96.5%) cases involved more than one substance.

“The resemblance of cannabis edibles, implicated in the majority of poisonings to candy, vitamins, and food products, is a risk to patients across the life span who may not fully understand what they are consuming or how potent it is,” Dr. Klein said in an interview.

Overall, nearly 1 in 10 exposures resulted in death or other major outcomes (life-threatening outcomes or outcomes involving major residual disability or disfigurement). For older adults, 19.4% of exposures led to death or other major harm.

“Elderly patients may also have comorbid conditions and polypharmacy, which contributes to their much more serious outcomes from cannabis poisoning,” Dr. Klein said.

The researchers caution that, owing to the cross-sectional nature of the data, they could not identify a causal association between cannabis use and suicide attempt.

With more states legalizing cannabis use by adults, increases in cannabis use will likely persist.

“It is important to further examine the suspected association between cannabis use and suicidal behaviors and how risks can be prevented or mitigated,” the researchers note.

Dr. Klein encourages health care providers to ask patients whether they are using cannabis and how they obtain and store it.

“As with all medications and substances, storage is a key safety issue that is elicited during a careful history,” said Dr. Klein.

Support for the study was provided in part by funds provided for medical and biological research by the State of Washington Initiative Measure No. 171. Dr. Klein has disclosed no relevant financial relationships.

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

There have been increases in suspected suicidal cannabis exposures reported to U.S. poison control centers over the past 13 years. The increases were notable both during and after the pandemic and were highest among children and female persons.

Investigators examined closed cases of cannabis-related human exposures that were coded as intentional-suspected suicidal.

Of note, there was a statistically significant increase in cannabis poisonings in young children (5-13 years) in 2021, during the pandemic, compared with 2019, a prepandemic year (3.1% vs. 1.3%; P < .001), the researchers report.

“This may speak to both increased access to cannabis as well as poor mental health status during the pandemic period,” study investigator Tracy Klein, PhD, assistant director, Center for Cannabis Policy, Research and Outreach, Washington State University Vancouver, Mount Vista, said in an interview.

The study was published online  in JAMA Network Open.

Reports of intentional poisonings with cannabis increased by roughly 17% annually over the study period. Most cases occurred in recent years and involved individuals aged 14-64 years. Nearly all (96.5%) cases involved more than one substance.

“The resemblance of cannabis edibles, implicated in the majority of poisonings to candy, vitamins, and food products, is a risk to patients across the life span who may not fully understand what they are consuming or how potent it is,” Dr. Klein said in an interview.

Overall, nearly 1 in 10 exposures resulted in death or other major outcomes (life-threatening outcomes or outcomes involving major residual disability or disfigurement). For older adults, 19.4% of exposures led to death or other major harm.

“Elderly patients may also have comorbid conditions and polypharmacy, which contributes to their much more serious outcomes from cannabis poisoning,” Dr. Klein said.

The researchers caution that, owing to the cross-sectional nature of the data, they could not identify a causal association between cannabis use and suicide attempt.

With more states legalizing cannabis use by adults, increases in cannabis use will likely persist.

“It is important to further examine the suspected association between cannabis use and suicidal behaviors and how risks can be prevented or mitigated,” the researchers note.

Dr. Klein encourages health care providers to ask patients whether they are using cannabis and how they obtain and store it.

“As with all medications and substances, storage is a key safety issue that is elicited during a careful history,” said Dr. Klein.

Support for the study was provided in part by funds provided for medical and biological research by the State of Washington Initiative Measure No. 171. Dr. Klein has disclosed no relevant financial relationships.

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

There have been increases in suspected suicidal cannabis exposures reported to U.S. poison control centers over the past 13 years. The increases were notable both during and after the pandemic and were highest among children and female persons.

Investigators examined closed cases of cannabis-related human exposures that were coded as intentional-suspected suicidal.

Of note, there was a statistically significant increase in cannabis poisonings in young children (5-13 years) in 2021, during the pandemic, compared with 2019, a prepandemic year (3.1% vs. 1.3%; P < .001), the researchers report.

“This may speak to both increased access to cannabis as well as poor mental health status during the pandemic period,” study investigator Tracy Klein, PhD, assistant director, Center for Cannabis Policy, Research and Outreach, Washington State University Vancouver, Mount Vista, said in an interview.

The study was published online  in JAMA Network Open.

Reports of intentional poisonings with cannabis increased by roughly 17% annually over the study period. Most cases occurred in recent years and involved individuals aged 14-64 years. Nearly all (96.5%) cases involved more than one substance.

“The resemblance of cannabis edibles, implicated in the majority of poisonings to candy, vitamins, and food products, is a risk to patients across the life span who may not fully understand what they are consuming or how potent it is,” Dr. Klein said in an interview.

Overall, nearly 1 in 10 exposures resulted in death or other major outcomes (life-threatening outcomes or outcomes involving major residual disability or disfigurement). For older adults, 19.4% of exposures led to death or other major harm.

“Elderly patients may also have comorbid conditions and polypharmacy, which contributes to their much more serious outcomes from cannabis poisoning,” Dr. Klein said.

The researchers caution that, owing to the cross-sectional nature of the data, they could not identify a causal association between cannabis use and suicide attempt.

With more states legalizing cannabis use by adults, increases in cannabis use will likely persist.

“It is important to further examine the suspected association between cannabis use and suicidal behaviors and how risks can be prevented or mitigated,” the researchers note.

Dr. Klein encourages health care providers to ask patients whether they are using cannabis and how they obtain and store it.

“As with all medications and substances, storage is a key safety issue that is elicited during a careful history,” said Dr. Klein.

Support for the study was provided in part by funds provided for medical and biological research by the State of Washington Initiative Measure No. 171. Dr. Klein has disclosed no relevant financial relationships.

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

An unusual cause of ischemic stroke – the presence of structural bone and cartilage anomalies which cause mechanical stress to arteries supplying the brain – has been highlighted in a new case series.

These so-called “bony” strokes constitute a possible cause of recurrent ischemia in the same vascular territory as previous episodes, note the authors, led by Johanna Haertl, MD, Technical University of Munich.

“In patients with recurrent strokes in one vascular territory the presence of a symptomatic anatomic bone or cartilage anomaly may be considered as a differential diagnosis after sufficient exclusion of competing etiologies of an ischemic stroke,” they conclude.

“Due to the possibly high risk of stroke recurrence and potentially causative treatment options, bony strokes seem to be highly relevant for clinical practice,” they add.

The study was published online in the journal Stroke.

In their report, investigators explain that diagnosis of a bony stroke is based on a combination of imaging devices including CT, MRI, angiography, and sonography of brain-supplying vessels.

In addition to conventional static imaging, dynamic imaging modalities with the patients’ head in a fixed rotation or reclination has been shown to be useful as this enables the detection of a compressive effect on brain-supplying arteries caused by head movement.

They note that these bony strokes have been described previously – mainly as single case reports or small case series – but a systematic evaluation of each anatomical type of bony stroke is currently lacking.

For the current paper, the authors describe the identification and therapeutic workup of six patients with a bony stroke among 4,200 patients with ischemic stroke treated from January 2017 to March 2022 at their comprehensive stroke care center, constituting an incidence of 0.14%.

But they caution, “Given our retrospective study design, the method of patient acquisition, and the lack of systematic evaluation of bony strokes during acute stroke treatment, epidemiologic conclusions can be drawn only very carefully.”

In each of these six cases, the recurrent stroke was found to be caused by large-artery embolism from mechanical stress by bone or cartilage anomalies on arteries supplying the brain.

“Our case series aims to raise awareness for the rare entity of bony strokes, emphasizing the necessity to evaluate structural bone or cartilage lesions as a possible cause of ischemic stroke in patients with stroke recurrence of unknown cause in one vascular territory. We further aim on highlighting individual diagnostic and therapeutic options,” they state.

They note that it has previously been suggested that ischemic strokes based on bone or cartilage anomalies are more common in the relatively young patients with stroke, which is in line with their current patient data (mean age, 55 years), but this may reflect a selection bias.

A medical history with an association between changes in the head position and the occurrence of ischemic stroke may also raise awareness of the possibility of a bony stroke.

The authors outline treatment options for bony stroke, which they describe as diverse: They include conservative treatment, endovascular stenting, occlusion of the affected vessel, surgical bypass, and bone/cartilage removal.

From a pathophysiologic point of view, it seems reasonable to eliminate a causative lesion by surgical removal of the mechanical stressor, they note.

In cases of vascular stenting, they caution that the remainder of the mechanical stressor may provoke stent fracture and recurrent stroke, which occurred in two of their patients, a situation that may be observed more often in the future with the increasing use of vascular stenting.

The authors report that, compared with annual stroke rates in atrial fibrillation patients, stroke recurrence in this patient cohort ahead of definite treatment was high (cumulative 2.14 strokes per year). And as no patient had further ischemia after treatment, they argue that diagnosis and appropriate treatment of bony stroke may reduce or even eliminate the risk for future stroke recurrence.

They propose that for the diagnosis an exact medical history, with emphasis on a possible change of head position at the onset of stroke symptoms, is useful.  

Furthermore, previously acquired diagnostic scans including CT or MRI may be evaluated for a symptomatic vessel-bone or cartilage contact. Then, the additional application of dynamic imaging modalities, including dynamic ultrasound of brain-supplying vessels and CT-angiography, may be discussed.

“An appropriate diagnosis and the evaluation of individual and interdisciplinary treatment options seem crucial to prevent recurrent ischemic strokes. Future prospective trials seem mandatory to optimize patient care,” they conclude.

The study had no specific funding. Coauthor Jan S. Kirschke, MD, received research support from the German Research Foundation, Bonescreen, H2020 European Research Council, and Philips. The other authors report no relevant financial relationships.

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

An unusual cause of ischemic stroke – the presence of structural bone and cartilage anomalies which cause mechanical stress to arteries supplying the brain – has been highlighted in a new case series.

These so-called “bony” strokes constitute a possible cause of recurrent ischemia in the same vascular territory as previous episodes, note the authors, led by Johanna Haertl, MD, Technical University of Munich.

“In patients with recurrent strokes in one vascular territory the presence of a symptomatic anatomic bone or cartilage anomaly may be considered as a differential diagnosis after sufficient exclusion of competing etiologies of an ischemic stroke,” they conclude.

“Due to the possibly high risk of stroke recurrence and potentially causative treatment options, bony strokes seem to be highly relevant for clinical practice,” they add.

The study was published online in the journal Stroke.

In their report, investigators explain that diagnosis of a bony stroke is based on a combination of imaging devices including CT, MRI, angiography, and sonography of brain-supplying vessels.

In addition to conventional static imaging, dynamic imaging modalities with the patients’ head in a fixed rotation or reclination has been shown to be useful as this enables the detection of a compressive effect on brain-supplying arteries caused by head movement.

They note that these bony strokes have been described previously – mainly as single case reports or small case series – but a systematic evaluation of each anatomical type of bony stroke is currently lacking.

For the current paper, the authors describe the identification and therapeutic workup of six patients with a bony stroke among 4,200 patients with ischemic stroke treated from January 2017 to March 2022 at their comprehensive stroke care center, constituting an incidence of 0.14%.

But they caution, “Given our retrospective study design, the method of patient acquisition, and the lack of systematic evaluation of bony strokes during acute stroke treatment, epidemiologic conclusions can be drawn only very carefully.”

In each of these six cases, the recurrent stroke was found to be caused by large-artery embolism from mechanical stress by bone or cartilage anomalies on arteries supplying the brain.

“Our case series aims to raise awareness for the rare entity of bony strokes, emphasizing the necessity to evaluate structural bone or cartilage lesions as a possible cause of ischemic stroke in patients with stroke recurrence of unknown cause in one vascular territory. We further aim on highlighting individual diagnostic and therapeutic options,” they state.

They note that it has previously been suggested that ischemic strokes based on bone or cartilage anomalies are more common in the relatively young patients with stroke, which is in line with their current patient data (mean age, 55 years), but this may reflect a selection bias.

A medical history with an association between changes in the head position and the occurrence of ischemic stroke may also raise awareness of the possibility of a bony stroke.

The authors outline treatment options for bony stroke, which they describe as diverse: They include conservative treatment, endovascular stenting, occlusion of the affected vessel, surgical bypass, and bone/cartilage removal.

From a pathophysiologic point of view, it seems reasonable to eliminate a causative lesion by surgical removal of the mechanical stressor, they note.

In cases of vascular stenting, they caution that the remainder of the mechanical stressor may provoke stent fracture and recurrent stroke, which occurred in two of their patients, a situation that may be observed more often in the future with the increasing use of vascular stenting.

The authors report that, compared with annual stroke rates in atrial fibrillation patients, stroke recurrence in this patient cohort ahead of definite treatment was high (cumulative 2.14 strokes per year). And as no patient had further ischemia after treatment, they argue that diagnosis and appropriate treatment of bony stroke may reduce or even eliminate the risk for future stroke recurrence.

They propose that for the diagnosis an exact medical history, with emphasis on a possible change of head position at the onset of stroke symptoms, is useful.  

Furthermore, previously acquired diagnostic scans including CT or MRI may be evaluated for a symptomatic vessel-bone or cartilage contact. Then, the additional application of dynamic imaging modalities, including dynamic ultrasound of brain-supplying vessels and CT-angiography, may be discussed.

“An appropriate diagnosis and the evaluation of individual and interdisciplinary treatment options seem crucial to prevent recurrent ischemic strokes. Future prospective trials seem mandatory to optimize patient care,” they conclude.

The study had no specific funding. Coauthor Jan S. Kirschke, MD, received research support from the German Research Foundation, Bonescreen, H2020 European Research Council, and Philips. The other authors report no relevant financial relationships.

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

An unusual cause of ischemic stroke – the presence of structural bone and cartilage anomalies which cause mechanical stress to arteries supplying the brain – has been highlighted in a new case series.

These so-called “bony” strokes constitute a possible cause of recurrent ischemia in the same vascular territory as previous episodes, note the authors, led by Johanna Haertl, MD, Technical University of Munich.

“In patients with recurrent strokes in one vascular territory the presence of a symptomatic anatomic bone or cartilage anomaly may be considered as a differential diagnosis after sufficient exclusion of competing etiologies of an ischemic stroke,” they conclude.

“Due to the possibly high risk of stroke recurrence and potentially causative treatment options, bony strokes seem to be highly relevant for clinical practice,” they add.

The study was published online in the journal Stroke.

In their report, investigators explain that diagnosis of a bony stroke is based on a combination of imaging devices including CT, MRI, angiography, and sonography of brain-supplying vessels.

In addition to conventional static imaging, dynamic imaging modalities with the patients’ head in a fixed rotation or reclination has been shown to be useful as this enables the detection of a compressive effect on brain-supplying arteries caused by head movement.

They note that these bony strokes have been described previously – mainly as single case reports or small case series – but a systematic evaluation of each anatomical type of bony stroke is currently lacking.

For the current paper, the authors describe the identification and therapeutic workup of six patients with a bony stroke among 4,200 patients with ischemic stroke treated from January 2017 to March 2022 at their comprehensive stroke care center, constituting an incidence of 0.14%.

But they caution, “Given our retrospective study design, the method of patient acquisition, and the lack of systematic evaluation of bony strokes during acute stroke treatment, epidemiologic conclusions can be drawn only very carefully.”

In each of these six cases, the recurrent stroke was found to be caused by large-artery embolism from mechanical stress by bone or cartilage anomalies on arteries supplying the brain.

“Our case series aims to raise awareness for the rare entity of bony strokes, emphasizing the necessity to evaluate structural bone or cartilage lesions as a possible cause of ischemic stroke in patients with stroke recurrence of unknown cause in one vascular territory. We further aim on highlighting individual diagnostic and therapeutic options,” they state.

They note that it has previously been suggested that ischemic strokes based on bone or cartilage anomalies are more common in the relatively young patients with stroke, which is in line with their current patient data (mean age, 55 years), but this may reflect a selection bias.

A medical history with an association between changes in the head position and the occurrence of ischemic stroke may also raise awareness of the possibility of a bony stroke.

The authors outline treatment options for bony stroke, which they describe as diverse: They include conservative treatment, endovascular stenting, occlusion of the affected vessel, surgical bypass, and bone/cartilage removal.

From a pathophysiologic point of view, it seems reasonable to eliminate a causative lesion by surgical removal of the mechanical stressor, they note.

In cases of vascular stenting, they caution that the remainder of the mechanical stressor may provoke stent fracture and recurrent stroke, which occurred in two of their patients, a situation that may be observed more often in the future with the increasing use of vascular stenting.

The authors report that, compared with annual stroke rates in atrial fibrillation patients, stroke recurrence in this patient cohort ahead of definite treatment was high (cumulative 2.14 strokes per year). And as no patient had further ischemia after treatment, they argue that diagnosis and appropriate treatment of bony stroke may reduce or even eliminate the risk for future stroke recurrence.

They propose that for the diagnosis an exact medical history, with emphasis on a possible change of head position at the onset of stroke symptoms, is useful.  

Furthermore, previously acquired diagnostic scans including CT or MRI may be evaluated for a symptomatic vessel-bone or cartilage contact. Then, the additional application of dynamic imaging modalities, including dynamic ultrasound of brain-supplying vessels and CT-angiography, may be discussed.

“An appropriate diagnosis and the evaluation of individual and interdisciplinary treatment options seem crucial to prevent recurrent ischemic strokes. Future prospective trials seem mandatory to optimize patient care,” they conclude.

The study had no specific funding. Coauthor Jan S. Kirschke, MD, received research support from the German Research Foundation, Bonescreen, H2020 European Research Council, and Philips. The other authors report no relevant financial relationships.

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

When weighing medical schools, Hannah Gewaid admits that she kept the annual rankings from U.S. News & World Report in mind. “If I could get into a school of higher prestige, then I could have better odds for a good residency placement,” the pre-med student at the University of California, San Diego, told this news organization.

Although Ms. Gewaid considered other factors, she ultimately chose the highest-ranked medical school to which she was accepted: Rocky Vista University, Ivins, Utah. But it was the school’s environment that appealed to her most, she said. “Medical school can be pretty cut-throat, and I felt like the community at Rocky Vista was supportive. They also have one of the highest pass rates for boards in the nation, so it felt like the right combination for me.”

Likewise, Ramie Fathy, MD, a PGY1 internal medicine resident at Pennsylvania Hospital, Philadelphia, considered the report’s rankings when applying to medical schools. He chose the Perelman School of Medicine at the University of Pennsylvania, which ranked fifth in the nation at the time, and graduated a year ago.

In January, Harvard Medical School pulled out of the popular U.S. News rankings that many students use to guide their application decisions. Soon afterwards, other top-ranked medical schools – Columbia and Stanford – dropped out, setting off a spate of hopeful medical students and physicians questioning the value of the rankings and prospective students’ reliance on them.

Although Dr. Fathy doesn’t regret selecting Perelman before it joined the list of exiting schools, he wonders if he was shortsighted using the rankings as criteria. “It’s hard to know what makes a school unique from others, and the rankings serve as a metric to guide you,” he said. “But in the end, it’s not a reliable or reflective way to judge a school.”

Dr. Fathy said he is proud that Perelman opted out of the rankings: “I think it will help ensure that they prioritize what is best for the students and the quality of their training, rather than aspects that are relevant to rankings but don’t translate to a better overall student experience.”

Dr. Fathy’s viewpoint seems to be shared by the medical schools that announced they will no longer participate in the U.S. News rankings. The Association of American Medical Colleges recently reported that more than a dozen of the top 20 medical schools in the 2023 report have publicly exited the rankings.

USNWR’s chairman and CEO Eric Gertler said in a prepared statement that students turn to the rankings for help in making a key career decision in the face of competitive admissions and high tuition costs.

“We know that comparing diverse academic institutions across a common data set is challenging, and that is why we have consistently stated that the rankings should be one component in a prospective student’s decision-making process.”

The schools’ reasons for exiting vary. In Harvard’s case, Dean George Q. Daley, MD, PhD, said in a statement that the rankings don’t align with the school’s high standards of the school’s medical education programs.

Critics of the rankings say they rely too much on the grades and test scores of accepted students, AAMC reported. Stanford Dean, Lloyd Minor, MD, said the rankings fail to “capture the full extent of what makes an exceptional learning environment.” A school’s mission, curriculum, and other metrics should also be used to judge educational value, he said.

Medical schools that publicly announced their decisions to withdraw from the rankings also pointed to the extensive time and resources needed to gather data to submit to USNWR, rise in the standings, and remain at the top.

Bryan Carmody, MD, a Norfolk, Va.-based pediatric nephrologist and pediatrics professor known for his medical school commentaries, said in an interview that he doesn’t see the value of the rankings. “If you look at the data and factors the report collects, it has almost no impact on the day-to-day experience and quality of the medical school. It doesn’t assess meaningful educational outputs.”

Using MCAT scores and the GPAs of incoming students is irrelevant to the value the school can provide a student, Dr. Carmody said.

“The stated idea of the rankings is to measure quality, but in reality, it’s to maintain a certain hierarchy,” he said. “The content of the MCAT is only peripherally relevant. Real patients don’t come in as a multiple-choice question.”

The withdrawal of Harvard – which held the top ranking – put the report’s shortcomings in the spotlight, Dr. Carmody said. But Harvard wasn’t the first to pull out. In 2016, the Uniformed Services University in Maryland exited the rankings. Some schools chose never to participate, including most Historically Black Colleges and Universities, as well as osteopathic medical schools.

Given the ripple effect of high-ranking schools like Harvard pulling out of the rankings, prospective students are left to find other criteria to measure their future med schools.
 

Weighing other factors

If he could apply again, Dr. Fathy said he has the experience to know he wouldn’t have put as much weight in the U.S. News rankings. “At the time I was applying, it was hard to understand exactly what the rankings stood for,” he said. “I thought maybe a higher ranking meant better research opportunities and better connections. It’s hard to let go of the prestige relative to it all.”

His final two options had been Penn or Stanford. “Penn was the better choice for me, not because of its rankings, but because I had unique mentors and research opportunities there, and also because I had a scholarship,” he said. “I also had no family on the West Coast, which would have made a difference had I chosen Stanford.”

Dr. Fathy is happy the rankings have lost some of their prestige.

“I’m hoping that as schools pull out, it will demonstrate to applicants that the rankings aren’t where they should focus,” he said. “I also hope that down the line, it will prevent the name of a school from being such a big factor in residency applications.”

Dr. Fathy added that applying to residency programs has been an inequitable process, as institutions seem to judge applicants based on where they went to medical school. “When you look at the match lists, I believe programs put preference on students coming out of higher-ranking institutions,” he said.

Ahmed Mukhtar Ahmed, MPP, MSc, who will graduate soon from Harvard Medical School, said he hopes that the withdrawals from the ranking system will benefit future students. His initial choice of Harvard wasn’t the result of the rankings, he said. His family came from Somalia in 1996. “My mom sacrificed so much for me to get where I am, and when I was choosing a school, Harvard was the only name she recognized. It meant so much for her that I was accepted here.”

Beyond the emotional tie-in, however, Mr. Ahmed found Harvard to be the right fit for other reasons. “There’s so much opportunity here for someone with a focus on public health, and it has served me well.”

Still, Mr. Ahmed was not ignorant of the rankings. “I don’t know too many students who didn’t have their fingers on the pulse of the rankings,” he said. “There’s awareness that it’s not a good metric, but when applying to residencies, they keep in mind where you went to med school. So, we all have it in the back of our minds, for better or worse.”

Like Dr. Fathy, Mr. Ahmed can see the cracks in the ranking system. “I think the exodus from the rankings is good for applicants and also for the landscape of institutions, in general,” he said. “There’s nothing that says the number-one school is the best school for you.”

Mr. Ahmed points to other criteria, including financing opportunities, when judging a prospective school. “Talk to students and ask about how responsive administration is should a concern pop up,” he said. “Are they invested in student well-being? Also look at the diversity of institutions and experiences you will have. That’s something I didn’t appreciate until I was a student. I learned new things from the different hospitals I rotated through.”
 

What the future holds

Dr. Carmody recommends that students determine what information about a school matters to them. “What is their residency placement like, for instance? Keep in mind that most schools don’t convey this entirely truthfully, but it’s a measurement.”

Mr. Ahmed points to the Medical School Admission Requirements database compiled by the AAMC. “Look in the database to filter out where you should apply without the numbers attached to it,” he said. “Look at the faculty-to-student ratio, how much debt you might have to take on, and what housing is like, for instance. We should move toward a weighing system like that, rather than rankings.”

If the withdrawals of medical schools eventually lead to the demise of the rankings, Dr. Carmody noted the downsides. “There’s some concern that this will hurt pre-med students because it was the one place to find a certain amount of credible, objective data. There’s a ring of truth to that and a worry that schools won’t provide data in any sort of standardized way for an apples-to-apples comparison.”

It would also take time – probably as much as a decade – for the legacy of the U.S. News rankings to completely disappear, according to Dr. Carmody. Dr. Fathy agrees. “The rankings are ingrained on so many levels,” he said. “The better the ranking, the better the funding, so it’s self-reinforcing.”

In the future, other factors should guide students’ decision-making, including distance from family and friends, available research opportunities, and whether students are happy at the school, Dr. Fathy said. “There are so many experiential points to consider that go beyond the flawed ranking system.”

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

When weighing medical schools, Hannah Gewaid admits that she kept the annual rankings from U.S. News & World Report in mind. “If I could get into a school of higher prestige, then I could have better odds for a good residency placement,” the pre-med student at the University of California, San Diego, told this news organization.

Although Ms. Gewaid considered other factors, she ultimately chose the highest-ranked medical school to which she was accepted: Rocky Vista University, Ivins, Utah. But it was the school’s environment that appealed to her most, she said. “Medical school can be pretty cut-throat, and I felt like the community at Rocky Vista was supportive. They also have one of the highest pass rates for boards in the nation, so it felt like the right combination for me.”

Likewise, Ramie Fathy, MD, a PGY1 internal medicine resident at Pennsylvania Hospital, Philadelphia, considered the report’s rankings when applying to medical schools. He chose the Perelman School of Medicine at the University of Pennsylvania, which ranked fifth in the nation at the time, and graduated a year ago.

In January, Harvard Medical School pulled out of the popular U.S. News rankings that many students use to guide their application decisions. Soon afterwards, other top-ranked medical schools – Columbia and Stanford – dropped out, setting off a spate of hopeful medical students and physicians questioning the value of the rankings and prospective students’ reliance on them.

Although Dr. Fathy doesn’t regret selecting Perelman before it joined the list of exiting schools, he wonders if he was shortsighted using the rankings as criteria. “It’s hard to know what makes a school unique from others, and the rankings serve as a metric to guide you,” he said. “But in the end, it’s not a reliable or reflective way to judge a school.”

Dr. Fathy said he is proud that Perelman opted out of the rankings: “I think it will help ensure that they prioritize what is best for the students and the quality of their training, rather than aspects that are relevant to rankings but don’t translate to a better overall student experience.”

Dr. Fathy’s viewpoint seems to be shared by the medical schools that announced they will no longer participate in the U.S. News rankings. The Association of American Medical Colleges recently reported that more than a dozen of the top 20 medical schools in the 2023 report have publicly exited the rankings.

USNWR’s chairman and CEO Eric Gertler said in a prepared statement that students turn to the rankings for help in making a key career decision in the face of competitive admissions and high tuition costs.

“We know that comparing diverse academic institutions across a common data set is challenging, and that is why we have consistently stated that the rankings should be one component in a prospective student’s decision-making process.”

The schools’ reasons for exiting vary. In Harvard’s case, Dean George Q. Daley, MD, PhD, said in a statement that the rankings don’t align with the school’s high standards of the school’s medical education programs.

Critics of the rankings say they rely too much on the grades and test scores of accepted students, AAMC reported. Stanford Dean, Lloyd Minor, MD, said the rankings fail to “capture the full extent of what makes an exceptional learning environment.” A school’s mission, curriculum, and other metrics should also be used to judge educational value, he said.

Medical schools that publicly announced their decisions to withdraw from the rankings also pointed to the extensive time and resources needed to gather data to submit to USNWR, rise in the standings, and remain at the top.

Bryan Carmody, MD, a Norfolk, Va.-based pediatric nephrologist and pediatrics professor known for his medical school commentaries, said in an interview that he doesn’t see the value of the rankings. “If you look at the data and factors the report collects, it has almost no impact on the day-to-day experience and quality of the medical school. It doesn’t assess meaningful educational outputs.”

Using MCAT scores and the GPAs of incoming students is irrelevant to the value the school can provide a student, Dr. Carmody said.

“The stated idea of the rankings is to measure quality, but in reality, it’s to maintain a certain hierarchy,” he said. “The content of the MCAT is only peripherally relevant. Real patients don’t come in as a multiple-choice question.”

The withdrawal of Harvard – which held the top ranking – put the report’s shortcomings in the spotlight, Dr. Carmody said. But Harvard wasn’t the first to pull out. In 2016, the Uniformed Services University in Maryland exited the rankings. Some schools chose never to participate, including most Historically Black Colleges and Universities, as well as osteopathic medical schools.

Given the ripple effect of high-ranking schools like Harvard pulling out of the rankings, prospective students are left to find other criteria to measure their future med schools.
 

Weighing other factors

If he could apply again, Dr. Fathy said he has the experience to know he wouldn’t have put as much weight in the U.S. News rankings. “At the time I was applying, it was hard to understand exactly what the rankings stood for,” he said. “I thought maybe a higher ranking meant better research opportunities and better connections. It’s hard to let go of the prestige relative to it all.”

His final two options had been Penn or Stanford. “Penn was the better choice for me, not because of its rankings, but because I had unique mentors and research opportunities there, and also because I had a scholarship,” he said. “I also had no family on the West Coast, which would have made a difference had I chosen Stanford.”

Dr. Fathy is happy the rankings have lost some of their prestige.

“I’m hoping that as schools pull out, it will demonstrate to applicants that the rankings aren’t where they should focus,” he said. “I also hope that down the line, it will prevent the name of a school from being such a big factor in residency applications.”

Dr. Fathy added that applying to residency programs has been an inequitable process, as institutions seem to judge applicants based on where they went to medical school. “When you look at the match lists, I believe programs put preference on students coming out of higher-ranking institutions,” he said.

Ahmed Mukhtar Ahmed, MPP, MSc, who will graduate soon from Harvard Medical School, said he hopes that the withdrawals from the ranking system will benefit future students. His initial choice of Harvard wasn’t the result of the rankings, he said. His family came from Somalia in 1996. “My mom sacrificed so much for me to get where I am, and when I was choosing a school, Harvard was the only name she recognized. It meant so much for her that I was accepted here.”

Beyond the emotional tie-in, however, Mr. Ahmed found Harvard to be the right fit for other reasons. “There’s so much opportunity here for someone with a focus on public health, and it has served me well.”

Still, Mr. Ahmed was not ignorant of the rankings. “I don’t know too many students who didn’t have their fingers on the pulse of the rankings,” he said. “There’s awareness that it’s not a good metric, but when applying to residencies, they keep in mind where you went to med school. So, we all have it in the back of our minds, for better or worse.”

Like Dr. Fathy, Mr. Ahmed can see the cracks in the ranking system. “I think the exodus from the rankings is good for applicants and also for the landscape of institutions, in general,” he said. “There’s nothing that says the number-one school is the best school for you.”

Mr. Ahmed points to other criteria, including financing opportunities, when judging a prospective school. “Talk to students and ask about how responsive administration is should a concern pop up,” he said. “Are they invested in student well-being? Also look at the diversity of institutions and experiences you will have. That’s something I didn’t appreciate until I was a student. I learned new things from the different hospitals I rotated through.”
 

What the future holds

Dr. Carmody recommends that students determine what information about a school matters to them. “What is their residency placement like, for instance? Keep in mind that most schools don’t convey this entirely truthfully, but it’s a measurement.”

Mr. Ahmed points to the Medical School Admission Requirements database compiled by the AAMC. “Look in the database to filter out where you should apply without the numbers attached to it,” he said. “Look at the faculty-to-student ratio, how much debt you might have to take on, and what housing is like, for instance. We should move toward a weighing system like that, rather than rankings.”

If the withdrawals of medical schools eventually lead to the demise of the rankings, Dr. Carmody noted the downsides. “There’s some concern that this will hurt pre-med students because it was the one place to find a certain amount of credible, objective data. There’s a ring of truth to that and a worry that schools won’t provide data in any sort of standardized way for an apples-to-apples comparison.”

It would also take time – probably as much as a decade – for the legacy of the U.S. News rankings to completely disappear, according to Dr. Carmody. Dr. Fathy agrees. “The rankings are ingrained on so many levels,” he said. “The better the ranking, the better the funding, so it’s self-reinforcing.”

In the future, other factors should guide students’ decision-making, including distance from family and friends, available research opportunities, and whether students are happy at the school, Dr. Fathy said. “There are so many experiential points to consider that go beyond the flawed ranking system.”

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

When weighing medical schools, Hannah Gewaid admits that she kept the annual rankings from U.S. News & World Report in mind. “If I could get into a school of higher prestige, then I could have better odds for a good residency placement,” the pre-med student at the University of California, San Diego, told this news organization.

Although Ms. Gewaid considered other factors, she ultimately chose the highest-ranked medical school to which she was accepted: Rocky Vista University, Ivins, Utah. But it was the school’s environment that appealed to her most, she said. “Medical school can be pretty cut-throat, and I felt like the community at Rocky Vista was supportive. They also have one of the highest pass rates for boards in the nation, so it felt like the right combination for me.”

Likewise, Ramie Fathy, MD, a PGY1 internal medicine resident at Pennsylvania Hospital, Philadelphia, considered the report’s rankings when applying to medical schools. He chose the Perelman School of Medicine at the University of Pennsylvania, which ranked fifth in the nation at the time, and graduated a year ago.

In January, Harvard Medical School pulled out of the popular U.S. News rankings that many students use to guide their application decisions. Soon afterwards, other top-ranked medical schools – Columbia and Stanford – dropped out, setting off a spate of hopeful medical students and physicians questioning the value of the rankings and prospective students’ reliance on them.

Although Dr. Fathy doesn’t regret selecting Perelman before it joined the list of exiting schools, he wonders if he was shortsighted using the rankings as criteria. “It’s hard to know what makes a school unique from others, and the rankings serve as a metric to guide you,” he said. “But in the end, it’s not a reliable or reflective way to judge a school.”

Dr. Fathy said he is proud that Perelman opted out of the rankings: “I think it will help ensure that they prioritize what is best for the students and the quality of their training, rather than aspects that are relevant to rankings but don’t translate to a better overall student experience.”

Dr. Fathy’s viewpoint seems to be shared by the medical schools that announced they will no longer participate in the U.S. News rankings. The Association of American Medical Colleges recently reported that more than a dozen of the top 20 medical schools in the 2023 report have publicly exited the rankings.

USNWR’s chairman and CEO Eric Gertler said in a prepared statement that students turn to the rankings for help in making a key career decision in the face of competitive admissions and high tuition costs.

“We know that comparing diverse academic institutions across a common data set is challenging, and that is why we have consistently stated that the rankings should be one component in a prospective student’s decision-making process.”

The schools’ reasons for exiting vary. In Harvard’s case, Dean George Q. Daley, MD, PhD, said in a statement that the rankings don’t align with the school’s high standards of the school’s medical education programs.

Critics of the rankings say they rely too much on the grades and test scores of accepted students, AAMC reported. Stanford Dean, Lloyd Minor, MD, said the rankings fail to “capture the full extent of what makes an exceptional learning environment.” A school’s mission, curriculum, and other metrics should also be used to judge educational value, he said.

Medical schools that publicly announced their decisions to withdraw from the rankings also pointed to the extensive time and resources needed to gather data to submit to USNWR, rise in the standings, and remain at the top.

Bryan Carmody, MD, a Norfolk, Va.-based pediatric nephrologist and pediatrics professor known for his medical school commentaries, said in an interview that he doesn’t see the value of the rankings. “If you look at the data and factors the report collects, it has almost no impact on the day-to-day experience and quality of the medical school. It doesn’t assess meaningful educational outputs.”

Using MCAT scores and the GPAs of incoming students is irrelevant to the value the school can provide a student, Dr. Carmody said.

“The stated idea of the rankings is to measure quality, but in reality, it’s to maintain a certain hierarchy,” he said. “The content of the MCAT is only peripherally relevant. Real patients don’t come in as a multiple-choice question.”

The withdrawal of Harvard – which held the top ranking – put the report’s shortcomings in the spotlight, Dr. Carmody said. But Harvard wasn’t the first to pull out. In 2016, the Uniformed Services University in Maryland exited the rankings. Some schools chose never to participate, including most Historically Black Colleges and Universities, as well as osteopathic medical schools.

Given the ripple effect of high-ranking schools like Harvard pulling out of the rankings, prospective students are left to find other criteria to measure their future med schools.
 

Weighing other factors

If he could apply again, Dr. Fathy said he has the experience to know he wouldn’t have put as much weight in the U.S. News rankings. “At the time I was applying, it was hard to understand exactly what the rankings stood for,” he said. “I thought maybe a higher ranking meant better research opportunities and better connections. It’s hard to let go of the prestige relative to it all.”

His final two options had been Penn or Stanford. “Penn was the better choice for me, not because of its rankings, but because I had unique mentors and research opportunities there, and also because I had a scholarship,” he said. “I also had no family on the West Coast, which would have made a difference had I chosen Stanford.”

Dr. Fathy is happy the rankings have lost some of their prestige.

“I’m hoping that as schools pull out, it will demonstrate to applicants that the rankings aren’t where they should focus,” he said. “I also hope that down the line, it will prevent the name of a school from being such a big factor in residency applications.”

Dr. Fathy added that applying to residency programs has been an inequitable process, as institutions seem to judge applicants based on where they went to medical school. “When you look at the match lists, I believe programs put preference on students coming out of higher-ranking institutions,” he said.

Ahmed Mukhtar Ahmed, MPP, MSc, who will graduate soon from Harvard Medical School, said he hopes that the withdrawals from the ranking system will benefit future students. His initial choice of Harvard wasn’t the result of the rankings, he said. His family came from Somalia in 1996. “My mom sacrificed so much for me to get where I am, and when I was choosing a school, Harvard was the only name she recognized. It meant so much for her that I was accepted here.”

Beyond the emotional tie-in, however, Mr. Ahmed found Harvard to be the right fit for other reasons. “There’s so much opportunity here for someone with a focus on public health, and it has served me well.”

Still, Mr. Ahmed was not ignorant of the rankings. “I don’t know too many students who didn’t have their fingers on the pulse of the rankings,” he said. “There’s awareness that it’s not a good metric, but when applying to residencies, they keep in mind where you went to med school. So, we all have it in the back of our minds, for better or worse.”

Like Dr. Fathy, Mr. Ahmed can see the cracks in the ranking system. “I think the exodus from the rankings is good for applicants and also for the landscape of institutions, in general,” he said. “There’s nothing that says the number-one school is the best school for you.”

Mr. Ahmed points to other criteria, including financing opportunities, when judging a prospective school. “Talk to students and ask about how responsive administration is should a concern pop up,” he said. “Are they invested in student well-being? Also look at the diversity of institutions and experiences you will have. That’s something I didn’t appreciate until I was a student. I learned new things from the different hospitals I rotated through.”
 

What the future holds

Dr. Carmody recommends that students determine what information about a school matters to them. “What is their residency placement like, for instance? Keep in mind that most schools don’t convey this entirely truthfully, but it’s a measurement.”

Mr. Ahmed points to the Medical School Admission Requirements database compiled by the AAMC. “Look in the database to filter out where you should apply without the numbers attached to it,” he said. “Look at the faculty-to-student ratio, how much debt you might have to take on, and what housing is like, for instance. We should move toward a weighing system like that, rather than rankings.”

If the withdrawals of medical schools eventually lead to the demise of the rankings, Dr. Carmody noted the downsides. “There’s some concern that this will hurt pre-med students because it was the one place to find a certain amount of credible, objective data. There’s a ring of truth to that and a worry that schools won’t provide data in any sort of standardized way for an apples-to-apples comparison.”

It would also take time – probably as much as a decade – for the legacy of the U.S. News rankings to completely disappear, according to Dr. Carmody. Dr. Fathy agrees. “The rankings are ingrained on so many levels,” he said. “The better the ranking, the better the funding, so it’s self-reinforcing.”

In the future, other factors should guide students’ decision-making, including distance from family and friends, available research opportunities, and whether students are happy at the school, Dr. Fathy said. “There are so many experiential points to consider that go beyond the flawed ranking system.”

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

In a phase 2 clinical trial of a potential treatment for fatigue associated with long COVID-19, people who received the medicine reported positive results over those receiving a placebo.

The study was conducted by researchers at the University of Oxford, England, and published in eClinical Medicine.

It was one of the first randomized double-blind placebo controlled trial for a possible treatment for long COVID, according to a press release from the university. 

“People living with long COVID in the trial who received AXA1125 had a significant improvement in fatigue compared to those who received a placebo,” the university reported.

Forty-one people participated. They had fatigue for 18 months beforehand. All completed the study, and none reported serious side effects.

AXA1125 was developed by U.S. pharmaceutical company Axcella Therapeutics.

“Potential causes [of long COVID fatigue] include reduced mitochondrial function and cellular bioenergetics,” the researchers reported.

“AXA1125 was tested in long COVID fatigue as previous data from Axcella showed effects on cellular energetics and inflammation. Emerging data on long COVID suggests that the virus targets the mitochondrial, which are essential to normal energy generation and control of inflammation,” the university noted in its press release. “AXA1125 may improve energy generation and reduce the amount of inflammation in the body.”

The study’s authors wrote that AXA1125 was tied to a “significant reduction in 28-day Chalder Fatigue Questionnaire score relative to placebo.” They said participants who reported less fatigue also had better mitochondrial health and walked farther in a 6-minute test.
 

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

In a phase 2 clinical trial of a potential treatment for fatigue associated with long COVID-19, people who received the medicine reported positive results over those receiving a placebo.

The study was conducted by researchers at the University of Oxford, England, and published in eClinical Medicine.

It was one of the first randomized double-blind placebo controlled trial for a possible treatment for long COVID, according to a press release from the university. 

“People living with long COVID in the trial who received AXA1125 had a significant improvement in fatigue compared to those who received a placebo,” the university reported.

Forty-one people participated. They had fatigue for 18 months beforehand. All completed the study, and none reported serious side effects.

AXA1125 was developed by U.S. pharmaceutical company Axcella Therapeutics.

“Potential causes [of long COVID fatigue] include reduced mitochondrial function and cellular bioenergetics,” the researchers reported.

“AXA1125 was tested in long COVID fatigue as previous data from Axcella showed effects on cellular energetics and inflammation. Emerging data on long COVID suggests that the virus targets the mitochondrial, which are essential to normal energy generation and control of inflammation,” the university noted in its press release. “AXA1125 may improve energy generation and reduce the amount of inflammation in the body.”

The study’s authors wrote that AXA1125 was tied to a “significant reduction in 28-day Chalder Fatigue Questionnaire score relative to placebo.” They said participants who reported less fatigue also had better mitochondrial health and walked farther in a 6-minute test.
 

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

In a phase 2 clinical trial of a potential treatment for fatigue associated with long COVID-19, people who received the medicine reported positive results over those receiving a placebo.

The study was conducted by researchers at the University of Oxford, England, and published in eClinical Medicine.

It was one of the first randomized double-blind placebo controlled trial for a possible treatment for long COVID, according to a press release from the university. 

“People living with long COVID in the trial who received AXA1125 had a significant improvement in fatigue compared to those who received a placebo,” the university reported.

Forty-one people participated. They had fatigue for 18 months beforehand. All completed the study, and none reported serious side effects.

AXA1125 was developed by U.S. pharmaceutical company Axcella Therapeutics.

“Potential causes [of long COVID fatigue] include reduced mitochondrial function and cellular bioenergetics,” the researchers reported.

“AXA1125 was tested in long COVID fatigue as previous data from Axcella showed effects on cellular energetics and inflammation. Emerging data on long COVID suggests that the virus targets the mitochondrial, which are essential to normal energy generation and control of inflammation,” the university noted in its press release. “AXA1125 may improve energy generation and reduce the amount of inflammation in the body.”

The study’s authors wrote that AXA1125 was tied to a “significant reduction in 28-day Chalder Fatigue Questionnaire score relative to placebo.” They said participants who reported less fatigue also had better mitochondrial health and walked farther in a 6-minute test.
 

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

People with type 2 diabetes are more likely than the general population to have a comorbid mental health disorder such as anxiety, depression, or eating disorders. Yet, only about one third receive treatment for these conditions.  

Untreated mental health disorders undermine quality of life and put this population at increased risk for poor self-care behaviors and suboptimal glycemic control.  

In this ReCAP, Mark Heyman, PhD, founder and director of the Center for Diabetes & Mental Health in San Diego, explains how diabetes burnout and distress undermine physical health for patients with type 2 diabetes. He emphasizes the importance of psychological support, and outlines screening tools to assess mental health in these patients. 

--

Mark Heyman, PhD, Psychologist, Center for Diabetes & Mental Health, San Diego, California 

Mark Heyman, PhD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Dexcom 

Received income in an amount equal to or greater than $250 from: Vertex; MannKind; Insulet 

People with type 2 diabetes are more likely than the general population to have a comorbid mental health disorder such as anxiety, depression, or eating disorders. Yet, only about one third receive treatment for these conditions.  

Untreated mental health disorders undermine quality of life and put this population at increased risk for poor self-care behaviors and suboptimal glycemic control.  

In this ReCAP, Mark Heyman, PhD, founder and director of the Center for Diabetes & Mental Health in San Diego, explains how diabetes burnout and distress undermine physical health for patients with type 2 diabetes. He emphasizes the importance of psychological support, and outlines screening tools to assess mental health in these patients. 

--

Mark Heyman, PhD, Psychologist, Center for Diabetes & Mental Health, San Diego, California 

Mark Heyman, PhD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Dexcom 

Received income in an amount equal to or greater than $250 from: Vertex; MannKind; Insulet 

People with type 2 diabetes are more likely than the general population to have a comorbid mental health disorder such as anxiety, depression, or eating disorders. Yet, only about one third receive treatment for these conditions.  

Untreated mental health disorders undermine quality of life and put this population at increased risk for poor self-care behaviors and suboptimal glycemic control.  

In this ReCAP, Mark Heyman, PhD, founder and director of the Center for Diabetes & Mental Health in San Diego, explains how diabetes burnout and distress undermine physical health for patients with type 2 diabetes. He emphasizes the importance of psychological support, and outlines screening tools to assess mental health in these patients. 

--

Mark Heyman, PhD, Psychologist, Center for Diabetes & Mental Health, San Diego, California 

Mark Heyman, PhD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Dexcom 

Received income in an amount equal to or greater than $250 from: Vertex; MannKind; Insulet 

COVID can more than triple the chance of being diagnosed with type 2 diabetes within a year of being infected, according to a new Canadian study.

Men who had even a mild case of COVID were significantly more likely than were noninfected men to be diagnosed with type 2 diabetes. Women didn’t have an increased risk unless they were severely ill.

Both men and women who had severe cases were at the highest risk. People who were hospitalized for COVID treatment had more than a doubled risk of being diagnosed with type 2 diabetes, and those who were admitted to intensive care units had more than a tripled risk.

“This is definitely a concern in terms of long-term outcomes,” researcher and University of British Columbia professor Naveed Z. Janjua, PhD, told The New York Times. “With a respiratory infection, you usually think, ‘Seven or eight days and I’m done with it, that’s it.’ [But] here we’re seeing lingering effects that are lifelong.”

The study was published in JAMA Network Open. Researchers analyzed health data from 2020 and 2021 for 629,935 people, 20% of whom were diagnosed with COVID during that time. Most people in the study had not been vaccinated because vaccines were not widely available then. The health information came from a registry maintained by public health officials in British Columbia. The follow-up period was 257 days.

The authors cautioned that their findings could not say that COVID causes type 2 diabetes; rather, in a commentary published along with the study, Pamela B. Davis, MD, PhD, said the link makes sense because COVID is known to impact the pancreas.

“Such a stress may move a patient from a prediabetic state into diabetes,” wrote Dr. Davis, former dean of Case Western Reserve University, Cleveland, where she is now a professor.

The researchers estimated that the increased pattern of diagnoses of diabetes following COVID infection could increase the rate of the disease occurring in the general population by 3%-5% overall.
 

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

COVID can more than triple the chance of being diagnosed with type 2 diabetes within a year of being infected, according to a new Canadian study.

Men who had even a mild case of COVID were significantly more likely than were noninfected men to be diagnosed with type 2 diabetes. Women didn’t have an increased risk unless they were severely ill.

Both men and women who had severe cases were at the highest risk. People who were hospitalized for COVID treatment had more than a doubled risk of being diagnosed with type 2 diabetes, and those who were admitted to intensive care units had more than a tripled risk.

“This is definitely a concern in terms of long-term outcomes,” researcher and University of British Columbia professor Naveed Z. Janjua, PhD, told The New York Times. “With a respiratory infection, you usually think, ‘Seven or eight days and I’m done with it, that’s it.’ [But] here we’re seeing lingering effects that are lifelong.”

The study was published in JAMA Network Open. Researchers analyzed health data from 2020 and 2021 for 629,935 people, 20% of whom were diagnosed with COVID during that time. Most people in the study had not been vaccinated because vaccines were not widely available then. The health information came from a registry maintained by public health officials in British Columbia. The follow-up period was 257 days.

The authors cautioned that their findings could not say that COVID causes type 2 diabetes; rather, in a commentary published along with the study, Pamela B. Davis, MD, PhD, said the link makes sense because COVID is known to impact the pancreas.

“Such a stress may move a patient from a prediabetic state into diabetes,” wrote Dr. Davis, former dean of Case Western Reserve University, Cleveland, where she is now a professor.

The researchers estimated that the increased pattern of diagnoses of diabetes following COVID infection could increase the rate of the disease occurring in the general population by 3%-5% overall.
 

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

COVID can more than triple the chance of being diagnosed with type 2 diabetes within a year of being infected, according to a new Canadian study.

Men who had even a mild case of COVID were significantly more likely than were noninfected men to be diagnosed with type 2 diabetes. Women didn’t have an increased risk unless they were severely ill.

Both men and women who had severe cases were at the highest risk. People who were hospitalized for COVID treatment had more than a doubled risk of being diagnosed with type 2 diabetes, and those who were admitted to intensive care units had more than a tripled risk.

“This is definitely a concern in terms of long-term outcomes,” researcher and University of British Columbia professor Naveed Z. Janjua, PhD, told The New York Times. “With a respiratory infection, you usually think, ‘Seven or eight days and I’m done with it, that’s it.’ [But] here we’re seeing lingering effects that are lifelong.”

The study was published in JAMA Network Open. Researchers analyzed health data from 2020 and 2021 for 629,935 people, 20% of whom were diagnosed with COVID during that time. Most people in the study had not been vaccinated because vaccines were not widely available then. The health information came from a registry maintained by public health officials in British Columbia. The follow-up period was 257 days.

The authors cautioned that their findings could not say that COVID causes type 2 diabetes; rather, in a commentary published along with the study, Pamela B. Davis, MD, PhD, said the link makes sense because COVID is known to impact the pancreas.

“Such a stress may move a patient from a prediabetic state into diabetes,” wrote Dr. Davis, former dean of Case Western Reserve University, Cleveland, where she is now a professor.

The researchers estimated that the increased pattern of diagnoses of diabetes following COVID infection could increase the rate of the disease occurring in the general population by 3%-5% overall.
 

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

WASHINGTON – A group therapy suicide prevention program for veterans delivered via telehealth is feasible and acceptable, new research shows.

Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.

“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Trial run

Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.

The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.

The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.

Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.

In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.

The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.

Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.

To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
 

High ratings

Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.

Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).

Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.

They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.

In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.

“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”

Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”

Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
 

Hopeful results

Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.

“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a  professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.

The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”

This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.

“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.

However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”

The researchers and Dr. Holtzheimer report no relevant financial relationships.

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

WASHINGTON – A group therapy suicide prevention program for veterans delivered via telehealth is feasible and acceptable, new research shows.

Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.

“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Trial run

Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.

The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.

The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.

Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.

In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.

The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.

Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.

To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
 

High ratings

Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.

Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).

Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.

They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.

In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.

“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”

Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”

Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
 

Hopeful results

Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.

“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a  professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.

The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”

This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.

“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.

However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”

The researchers and Dr. Holtzheimer report no relevant financial relationships.

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

WASHINGTON – A group therapy suicide prevention program for veterans delivered via telehealth is feasible and acceptable, new research shows.

Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.

“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Trial run

Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.

The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.

The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.

Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.

In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.

The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.

Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.

To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
 

High ratings

Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.

Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).

Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.

They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.

In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.

“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”

Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”

Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
 

Hopeful results

Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.

“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a  professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.

The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”

This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.

“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.

However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”

The researchers and Dr. Holtzheimer report no relevant financial relationships.

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

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years. 

Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.

Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer. 

The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision. 

The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.

The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less  immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.

DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:

• Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.

• Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues. 

• Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.

Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years. 

Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.

Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer. 

The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision. 

The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.

The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less  immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.

DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:

• Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.

• Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues. 

• Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.

Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years. 

Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.

Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer. 

The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision. 

The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.

The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less  immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.

DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:

• Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.

• Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues. 

• Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.

Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.