Moderate, severe, and penetrating traumatic brain injury (TBI) is associated with an elevated risk of developing brain cancer, new research suggested. However, mild TBI appears to confer no increased risk.

In a large cohort of post-9/11 US veterans, those who suffered moderate/severe TBI had a nearly twofold increased risk for a subsequent brain cancer diagnosis, while those with penetrating TBI had a greater than threefold increased risk.

“While the absolute number of brain cancer diagnoses was small, these diagnoses are associated with profoundly poor outcomes. Further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols,” wrote investigators led by Ian Stewart, MD, with the Uniformed Services University of Health Sciences, Bethesda, Maryland.

The study was published online on February 15 in JAMA Network Open.
 

Common War Wound

TBI is one of the most common battlefield wounds among veterans of the Iraq and Afghanistan wars. But evidence to date on the potential association of TBI with the subsequent risk for brain cancer is conflicting, the authors noted.

To investigate further, they reviewed the records of nearly 2 million mostly male US veterans of the Iraq and Afghanistan wars. A total of 449,880 people experienced TBI, which was mild in 385,848 cases, moderate/severe in 46,859 cases, and penetrating in 17,173 cases.

During a median follow-up of 7.2 years, brain cancer occurred in 318 veterans without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (0.06% or less).

There was a stepwise increase in brain cancer incidence with worse TBI severity. Crude incidence rates per 100,000 person-years were 3.06 for no TBI, 2.85 for mild TBI, 4.88 for moderate/severe TBI, and 10.34 for penetrating TBI.

In the fully adjusted model, moderate/severe TBI showed a near-doubling of brain cancer risk vs no TBI (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.16-3.12), while penetrating TBI was associated with a greater than tripling of risk (aHR, 3.33; 95% CI, 1.71-6.49). There was no significantly increased risk after mild TBI.

There are plausible biological mechanisms linking TBI to brain cancer, the authors noted, including alterations in metabolism, inflammation, astrocyte proliferation, and stem cell migration and differentiation.

They caution that with few female veterans and a predominantly young cohort, the findings may not extend to the general population.
 

Meaningful New Data 

In an accompanying editorial, Elie Massaad, MD, MSc, and Ali Kiapour, PhD, MMSc, Massachusetts General Hospital, Boston, noted that federal data show glioblastoma, the most aggressive malignant brain tumor, is the third leading cause of cancer-related death among active duty personnel.

“Post-9/11 veterans deployed to Iraq, Afghanistan, and elsewhere face a 26% higher glioblastoma rate vs the general public, with an average age of onset decades earlier than in broader populations,” they wrote.

Overall, they noted this new research provides “meaningful data clarifying associations between combat-related TBI severity and subsequent brain cancer risk among post-9/11 veterans.

“Elucidating potential connections between battlefield trauma and longer-term health outcomes is imperative to inform prevention and care approaches for those who have served,” they added.

This study was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military Relevant Brain Injury Consortium. The authors and editorialists had declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Moderate, severe, and penetrating traumatic brain injury (TBI) is associated with an elevated risk of developing brain cancer, new research suggested. However, mild TBI appears to confer no increased risk.

In a large cohort of post-9/11 US veterans, those who suffered moderate/severe TBI had a nearly twofold increased risk for a subsequent brain cancer diagnosis, while those with penetrating TBI had a greater than threefold increased risk.

“While the absolute number of brain cancer diagnoses was small, these diagnoses are associated with profoundly poor outcomes. Further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols,” wrote investigators led by Ian Stewart, MD, with the Uniformed Services University of Health Sciences, Bethesda, Maryland.

The study was published online on February 15 in JAMA Network Open.
 

Common War Wound

TBI is one of the most common battlefield wounds among veterans of the Iraq and Afghanistan wars. But evidence to date on the potential association of TBI with the subsequent risk for brain cancer is conflicting, the authors noted.

To investigate further, they reviewed the records of nearly 2 million mostly male US veterans of the Iraq and Afghanistan wars. A total of 449,880 people experienced TBI, which was mild in 385,848 cases, moderate/severe in 46,859 cases, and penetrating in 17,173 cases.

During a median follow-up of 7.2 years, brain cancer occurred in 318 veterans without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (0.06% or less).

There was a stepwise increase in brain cancer incidence with worse TBI severity. Crude incidence rates per 100,000 person-years were 3.06 for no TBI, 2.85 for mild TBI, 4.88 for moderate/severe TBI, and 10.34 for penetrating TBI.

In the fully adjusted model, moderate/severe TBI showed a near-doubling of brain cancer risk vs no TBI (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.16-3.12), while penetrating TBI was associated with a greater than tripling of risk (aHR, 3.33; 95% CI, 1.71-6.49). There was no significantly increased risk after mild TBI.

There are plausible biological mechanisms linking TBI to brain cancer, the authors noted, including alterations in metabolism, inflammation, astrocyte proliferation, and stem cell migration and differentiation.

They caution that with few female veterans and a predominantly young cohort, the findings may not extend to the general population.
 

Meaningful New Data 

In an accompanying editorial, Elie Massaad, MD, MSc, and Ali Kiapour, PhD, MMSc, Massachusetts General Hospital, Boston, noted that federal data show glioblastoma, the most aggressive malignant brain tumor, is the third leading cause of cancer-related death among active duty personnel.

“Post-9/11 veterans deployed to Iraq, Afghanistan, and elsewhere face a 26% higher glioblastoma rate vs the general public, with an average age of onset decades earlier than in broader populations,” they wrote.

Overall, they noted this new research provides “meaningful data clarifying associations between combat-related TBI severity and subsequent brain cancer risk among post-9/11 veterans.

“Elucidating potential connections between battlefield trauma and longer-term health outcomes is imperative to inform prevention and care approaches for those who have served,” they added.

This study was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military Relevant Brain Injury Consortium. The authors and editorialists had declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Moderate, severe, and penetrating traumatic brain injury (TBI) is associated with an elevated risk of developing brain cancer, new research suggested. However, mild TBI appears to confer no increased risk.

In a large cohort of post-9/11 US veterans, those who suffered moderate/severe TBI had a nearly twofold increased risk for a subsequent brain cancer diagnosis, while those with penetrating TBI had a greater than threefold increased risk.

“While the absolute number of brain cancer diagnoses was small, these diagnoses are associated with profoundly poor outcomes. Further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols,” wrote investigators led by Ian Stewart, MD, with the Uniformed Services University of Health Sciences, Bethesda, Maryland.

The study was published online on February 15 in JAMA Network Open.
 

Common War Wound

TBI is one of the most common battlefield wounds among veterans of the Iraq and Afghanistan wars. But evidence to date on the potential association of TBI with the subsequent risk for brain cancer is conflicting, the authors noted.

To investigate further, they reviewed the records of nearly 2 million mostly male US veterans of the Iraq and Afghanistan wars. A total of 449,880 people experienced TBI, which was mild in 385,848 cases, moderate/severe in 46,859 cases, and penetrating in 17,173 cases.

During a median follow-up of 7.2 years, brain cancer occurred in 318 veterans without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (0.06% or less).

There was a stepwise increase in brain cancer incidence with worse TBI severity. Crude incidence rates per 100,000 person-years were 3.06 for no TBI, 2.85 for mild TBI, 4.88 for moderate/severe TBI, and 10.34 for penetrating TBI.

In the fully adjusted model, moderate/severe TBI showed a near-doubling of brain cancer risk vs no TBI (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.16-3.12), while penetrating TBI was associated with a greater than tripling of risk (aHR, 3.33; 95% CI, 1.71-6.49). There was no significantly increased risk after mild TBI.

There are plausible biological mechanisms linking TBI to brain cancer, the authors noted, including alterations in metabolism, inflammation, astrocyte proliferation, and stem cell migration and differentiation.

They caution that with few female veterans and a predominantly young cohort, the findings may not extend to the general population.
 

Meaningful New Data 

In an accompanying editorial, Elie Massaad, MD, MSc, and Ali Kiapour, PhD, MMSc, Massachusetts General Hospital, Boston, noted that federal data show glioblastoma, the most aggressive malignant brain tumor, is the third leading cause of cancer-related death among active duty personnel.

“Post-9/11 veterans deployed to Iraq, Afghanistan, and elsewhere face a 26% higher glioblastoma rate vs the general public, with an average age of onset decades earlier than in broader populations,” they wrote.

Overall, they noted this new research provides “meaningful data clarifying associations between combat-related TBI severity and subsequent brain cancer risk among post-9/11 veterans.

“Elucidating potential connections between battlefield trauma and longer-term health outcomes is imperative to inform prevention and care approaches for those who have served,” they added.

This study was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military Relevant Brain Injury Consortium. The authors and editorialists had declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Additionally, several recently published reviews have examined the risks of comorbidities that are not neurologic or cardiovascular, such as allergies, inflammatory bowel disease, obesity, and diabetes. Although these types of associations are not inherently obvious in terms of migraine pathophysiology, determining whether there is a link may help shed a light on some contributing factors that could play a role in migraine or in the comorbid disorders.

Authors of a study published in the January 2024 issue of the European Journal of Medical Research sought to examine the relationship between allergic rhinitis and migraine. They noted that several studies, as well as a statement from the American Migraine Prevalence and Prevention Study, published in 2013, reported an increased frequency of migraines in patients with allergic rhinitis. The researchers used data extracted from the UK Biobank, comprising 25,486 patients diagnosed with allergic rhinitis and 87,097 controls and 8547 migraine cases and 176,107 controls. They performed statistical analysis using bidirectional two-sample Mendelian randomization with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The researchers did not find any clear causal or genetic association between allergic rhinitis and migraine risk. However, the lack of causation between migraine and allergic rhinitis does not contradict previous studies that point to the prevalence of comorbidity of the two conditions. It's also important to note that congestion is a known migraine trigger, and the results of the study do not contradict that relationship. Given the variability of results from different research studies, the authors suggested that more research is warranted to help untangle the complex association between allergic rhinitis and migraine.

Inflammatory bowel disease (IBD) is another condition with a higher prevalence in patients who have migraine. A January 2024 article in Scientific Reports described the results of a nationwide population-based study that was conducted using data from the Korean National Health Insurance Service database. This study included 10,131,193 individuals. The researchers found that the risk for development of IBD in patients with migraine was significantly higher, by 1.3 times, compared with the general population. These results are similar to previous studies, such as a meta-analysis published in May 2023 in the International Journal of Preventive Medicine, which reported a pooled prevalence of migraine in IBD cases of 19%, with 1.5-fold higher odds of developing migraine in IBD cases when compared with controls.^[3] These studies were both aimed at examining epidemiologic data rather than uncovering a physiologic or genetic cause of the link, and neither study described an explanation for this connection.

A Mendelian randomization study published in May 2023 in Headache investigated potential genetic links between migraine and IBD. As with the January 2024 European Journal of Medical Research study that was done to search for a genetic association between migraine and allergic rhinitis, the authors stated that there was no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease.^[4] Although the evidence doesn't point to a causal relationship, it's important to note that diet plays a role in migraine management, and diet is especially important in managing IBD. Consideration of dietary factors could be beneficial for preventing symptoms — and is even more important for avoiding exacerbation of symptoms.

A high body mass index (BMI) is correlated with migraine. A study published in January 2024 in BMC Geriatrics analyzed data from people who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 by the Centers for Disease Control and the National Center for Health Statistics, comprising a total of 31,126 participants. The researchers found a linear association between BMI and migraine. They also noted that increased BMI was related to a significantly higher risk for migraine in the group with diabetes, but this positive relationship between BMI and migraine seemed to be smaller in the group without diabetes. The authors considered inflammation associated with obesity as a possible contributing factor for this link but acknowledged that the pathophysiologic mechanism is unknown and suggested that there is a high likelihood of confounding factors. Given that diabetes and obesity are both correlated with an increased risk for vascular disease and migraine is associated with a slight increase in cardiovascular risk, it could be especially important to identify these comorbidities in individual patients.

Migraine is common, and many comorbidities have been verified with population studies. Although there are some explanations for the links between migraine and vascular or neurologic conditions, the cause of associations between migraine and other conditions is not known. Some theories that have begun to be investigated include inflammation and genetics. Eventually, further research and understanding of contributing factors could potentially provide explanations that may help in diagnosing migraine or associated disorders at an early stage — and might even be used to help guide treatment.

Additional References

1. Ashina M, Katsarava Z, Do TP, et al. Migraine: Epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/S0140-6736(20)32160-7 Source

2. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631-649. doi: 10.1016/j.ncl.2019.06.001 Source

3. Olfati H, Mirmosayyeb O, Hosseinabadi AM, Ghajarzadeh M. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med. 2023;14:66. doi: 10.4103/ijpvm.ijpvm_413_21 Source

4. Welander NZ, Rukh G, Rask-Andersen M, Harder AV, et al and International Headache Genetics Consortium. Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study. Headache. 2023;63:642-651. doi: 10.1111/head.14470 Source

Additionally, several recently published reviews have examined the risks of comorbidities that are not neurologic or cardiovascular, such as allergies, inflammatory bowel disease, obesity, and diabetes. Although these types of associations are not inherently obvious in terms of migraine pathophysiology, determining whether there is a link may help shed a light on some contributing factors that could play a role in migraine or in the comorbid disorders.

Authors of a study published in the January 2024 issue of the European Journal of Medical Research sought to examine the relationship between allergic rhinitis and migraine. They noted that several studies, as well as a statement from the American Migraine Prevalence and Prevention Study, published in 2013, reported an increased frequency of migraines in patients with allergic rhinitis. The researchers used data extracted from the UK Biobank, comprising 25,486 patients diagnosed with allergic rhinitis and 87,097 controls and 8547 migraine cases and 176,107 controls. They performed statistical analysis using bidirectional two-sample Mendelian randomization with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The researchers did not find any clear causal or genetic association between allergic rhinitis and migraine risk. However, the lack of causation between migraine and allergic rhinitis does not contradict previous studies that point to the prevalence of comorbidity of the two conditions. It's also important to note that congestion is a known migraine trigger, and the results of the study do not contradict that relationship. Given the variability of results from different research studies, the authors suggested that more research is warranted to help untangle the complex association between allergic rhinitis and migraine.

Inflammatory bowel disease (IBD) is another condition with a higher prevalence in patients who have migraine. A January 2024 article in Scientific Reports described the results of a nationwide population-based study that was conducted using data from the Korean National Health Insurance Service database. This study included 10,131,193 individuals. The researchers found that the risk for development of IBD in patients with migraine was significantly higher, by 1.3 times, compared with the general population. These results are similar to previous studies, such as a meta-analysis published in May 2023 in the International Journal of Preventive Medicine, which reported a pooled prevalence of migraine in IBD cases of 19%, with 1.5-fold higher odds of developing migraine in IBD cases when compared with controls.^[3] These studies were both aimed at examining epidemiologic data rather than uncovering a physiologic or genetic cause of the link, and neither study described an explanation for this connection.

A Mendelian randomization study published in May 2023 in Headache investigated potential genetic links between migraine and IBD. As with the January 2024 European Journal of Medical Research study that was done to search for a genetic association between migraine and allergic rhinitis, the authors stated that there was no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease.^[4] Although the evidence doesn't point to a causal relationship, it's important to note that diet plays a role in migraine management, and diet is especially important in managing IBD. Consideration of dietary factors could be beneficial for preventing symptoms — and is even more important for avoiding exacerbation of symptoms.

A high body mass index (BMI) is correlated with migraine. A study published in January 2024 in BMC Geriatrics analyzed data from people who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 by the Centers for Disease Control and the National Center for Health Statistics, comprising a total of 31,126 participants. The researchers found a linear association between BMI and migraine. They also noted that increased BMI was related to a significantly higher risk for migraine in the group with diabetes, but this positive relationship between BMI and migraine seemed to be smaller in the group without diabetes. The authors considered inflammation associated with obesity as a possible contributing factor for this link but acknowledged that the pathophysiologic mechanism is unknown and suggested that there is a high likelihood of confounding factors. Given that diabetes and obesity are both correlated with an increased risk for vascular disease and migraine is associated with a slight increase in cardiovascular risk, it could be especially important to identify these comorbidities in individual patients.

Migraine is common, and many comorbidities have been verified with population studies. Although there are some explanations for the links between migraine and vascular or neurologic conditions, the cause of associations between migraine and other conditions is not known. Some theories that have begun to be investigated include inflammation and genetics. Eventually, further research and understanding of contributing factors could potentially provide explanations that may help in diagnosing migraine or associated disorders at an early stage — and might even be used to help guide treatment.

Additional References

1. Ashina M, Katsarava Z, Do TP, et al. Migraine: Epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/S0140-6736(20)32160-7 Source

2. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631-649. doi: 10.1016/j.ncl.2019.06.001 Source

3. Olfati H, Mirmosayyeb O, Hosseinabadi AM, Ghajarzadeh M. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med. 2023;14:66. doi: 10.4103/ijpvm.ijpvm_413_21 Source

4. Welander NZ, Rukh G, Rask-Andersen M, Harder AV, et al and International Headache Genetics Consortium. Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study. Headache. 2023;63:642-651. doi: 10.1111/head.14470 Source

Additionally, several recently published reviews have examined the risks of comorbidities that are not neurologic or cardiovascular, such as allergies, inflammatory bowel disease, obesity, and diabetes. Although these types of associations are not inherently obvious in terms of migraine pathophysiology, determining whether there is a link may help shed a light on some contributing factors that could play a role in migraine or in the comorbid disorders.

Authors of a study published in the January 2024 issue of the European Journal of Medical Research sought to examine the relationship between allergic rhinitis and migraine. They noted that several studies, as well as a statement from the American Migraine Prevalence and Prevention Study, published in 2013, reported an increased frequency of migraines in patients with allergic rhinitis. The researchers used data extracted from the UK Biobank, comprising 25,486 patients diagnosed with allergic rhinitis and 87,097 controls and 8547 migraine cases and 176,107 controls. They performed statistical analysis using bidirectional two-sample Mendelian randomization with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The researchers did not find any clear causal or genetic association between allergic rhinitis and migraine risk. However, the lack of causation between migraine and allergic rhinitis does not contradict previous studies that point to the prevalence of comorbidity of the two conditions. It's also important to note that congestion is a known migraine trigger, and the results of the study do not contradict that relationship. Given the variability of results from different research studies, the authors suggested that more research is warranted to help untangle the complex association between allergic rhinitis and migraine.

Inflammatory bowel disease (IBD) is another condition with a higher prevalence in patients who have migraine. A January 2024 article in Scientific Reports described the results of a nationwide population-based study that was conducted using data from the Korean National Health Insurance Service database. This study included 10,131,193 individuals. The researchers found that the risk for development of IBD in patients with migraine was significantly higher, by 1.3 times, compared with the general population. These results are similar to previous studies, such as a meta-analysis published in May 2023 in the International Journal of Preventive Medicine, which reported a pooled prevalence of migraine in IBD cases of 19%, with 1.5-fold higher odds of developing migraine in IBD cases when compared with controls.^[3] These studies were both aimed at examining epidemiologic data rather than uncovering a physiologic or genetic cause of the link, and neither study described an explanation for this connection.

A Mendelian randomization study published in May 2023 in Headache investigated potential genetic links between migraine and IBD. As with the January 2024 European Journal of Medical Research study that was done to search for a genetic association between migraine and allergic rhinitis, the authors stated that there was no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease.^[4] Although the evidence doesn't point to a causal relationship, it's important to note that diet plays a role in migraine management, and diet is especially important in managing IBD. Consideration of dietary factors could be beneficial for preventing symptoms — and is even more important for avoiding exacerbation of symptoms.

A high body mass index (BMI) is correlated with migraine. A study published in January 2024 in BMC Geriatrics analyzed data from people who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 by the Centers for Disease Control and the National Center for Health Statistics, comprising a total of 31,126 participants. The researchers found a linear association between BMI and migraine. They also noted that increased BMI was related to a significantly higher risk for migraine in the group with diabetes, but this positive relationship between BMI and migraine seemed to be smaller in the group without diabetes. The authors considered inflammation associated with obesity as a possible contributing factor for this link but acknowledged that the pathophysiologic mechanism is unknown and suggested that there is a high likelihood of confounding factors. Given that diabetes and obesity are both correlated with an increased risk for vascular disease and migraine is associated with a slight increase in cardiovascular risk, it could be especially important to identify these comorbidities in individual patients.

Migraine is common, and many comorbidities have been verified with population studies. Although there are some explanations for the links between migraine and vascular or neurologic conditions, the cause of associations between migraine and other conditions is not known. Some theories that have begun to be investigated include inflammation and genetics. Eventually, further research and understanding of contributing factors could potentially provide explanations that may help in diagnosing migraine or associated disorders at an early stage — and might even be used to help guide treatment.

Additional References

1. Ashina M, Katsarava Z, Do TP, et al. Migraine: Epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/S0140-6736(20)32160-7 Source

2. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631-649. doi: 10.1016/j.ncl.2019.06.001 Source

3. Olfati H, Mirmosayyeb O, Hosseinabadi AM, Ghajarzadeh M. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med. 2023;14:66. doi: 10.4103/ijpvm.ijpvm_413_21 Source

4. Welander NZ, Rukh G, Rask-Andersen M, Harder AV, et al and International Headache Genetics Consortium. Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study. Headache. 2023;63:642-651. doi: 10.1111/head.14470 Source

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

This study provides compelling evidence that a twice-daily dosing regimen of moderate-dose proton pump inhibitors (PPIs) is superior to a once-daily regimen for inducing histologic remission in eosinophilic esophagitis (EoE). This finding suggests a significant paradigm shift in EoE management, challenging the current standard treatment guideline that recommends a PPI trial of 20-40 mg twice daily. The limited data on various dosing regimens for EoE treatment underscores the importance of this research. Dr Muftah and colleagues from Brigham and Women's Hospital have conducted a novel retrospective cohort study to address the question: Does a twice-daily PPI dose induce a higher remission rate in EoE than a once-daily regimen does regardless of the total daily dose?

The study enrolled adult patients with newly-diagnosed treatment-naive EoE at a tertiary care center, dividing participants into four groups on the basis of their treatment regimen: once-daily standard dose (20 mg omeprazole), once-daily moderate dose (40 mg), twice-daily moderate dose (20 mg), and twice-daily high dose (40 mg). Patients underwent endoscopy 8-12 weeks after initiating PPI treatment, with the primary outcome being the histologic response to PPI, defined as fewer than 15 eosinophils/high power field in repeat esophageal biopsies.

Out of 305 patients (54.6% men, mean age 44.7 ± 16.7 years), 42.3% achieved a histologic response to PPI treatment. Patients receiving the standard PPI dose (20 mg omeprazole once daily) vs those on twice-daily moderate and high doses showed significantly higher histologic response rates (52.8% vs 11.8%, P < .0001; and 54.3% vs 11.8%, P < .0001; respectively). Multivariable analysis revealed that twice-daily moderate and high doses were significantly more effective (adjusted odds ration [aOR] 6.75; CI 2.53-18.0, P = .0008; and aOR 12.8, CI 4.69-34.8, P < .001; respectively).

However, the study's retrospective design limits its ability to establish causality and may introduce selection bias. In addition, the lack of specified adjustments for PPI dosing based on diet and lifestyle factors across the cohort could influence treatment response and outcomes. Last, as a single-center study, the results may not generalize across diverse patient populations, particularly those with different demographics or disease severities.

This research heralds a shift toward a more effective treatment strategy in EoE management, suggesting that a twice-daily PPI regimen may be more beneficial than once-daily dosing is for inducing histologic remission, especially in patients inadequately responding to once-daily PPI treatment. It advocates for a personalized treatment approach, considering factors such as symptom severity, previous PPI response, and potential for adherence to a twice-daily regimen.

Distinguishing between inflammatory bowel disease (IBD)–induced eosinophilia and EoE poses a significant challenge for clinicians. Given that the incidence of EoE is 3-5 times higher in patients with IBD compared with the general population, there is a pressing need for new biomarkers to differentiate between these two conditions. In response to this need, Dr Butzke and colleagues at Nemours Children's Health in Wilmington, Delaware, conducted a retrospective study to evaluate the roles of Major Basic Protein (MBP) and interleukin (IL)-13 in distinguishing these diseases. The study included participants who underwent esophagogastroduodenoscopy with esophageal biopsies for IBD workup or suspicion of EoE. It comprised 27 patients with EoE-IBD, 39 with EoE, 29 with IBD eosinophilia, 30 with IBD only, and 30 control patients. The biopsies were stained with MBP and IL-13 antibodies, and the results (percent staining/total tissue area), demographic, and clinical findings were compared among the groups.

The study revealed that MBP staining levels among patients with EoE-IBD were 3.8 units, which is significantly lower than those in the EoE group at 52.8 units and higher than those with IBD eosinophilia at 0.2 units (P < .001). IL-13 expression was significantly higher only compared with the IBD and control groups and not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity, whereas IL-13 demonstrated 83% sensitivity and 90% specificity using a cutoff point from the cohort of patients without EoE-IBD. Based on the MBP cutoff point of 3.49 units that distinguished between EoE and non-EoE cases, 100% of patients with EoE were MBP-positive compared with 3% of patients with IBD-associated eosinophilia (P < .05).

To implement this new biomarker into clinical practice, guidelines for interpreting MBP staining results should be developed and established, including defining cutoff points for positive and negative results. However, this study faces several limitations, such as not evaluating the differences in MBP results based on EoE-IBD type and disease activity. The retrospective nature of the study and its small sample size limit its power. In addition, the study did not assess how different treatments and disease activity affect MBP levels nor did it address the lack of longitudinal evaluation in assessing MBP levels.

Despite these limitations, the study presents a compelling case for the use of MBP as a biomarker to distinguish true EoE from EoE-IBD. This differentiation is crucial because it can guide therapeutic approaches, influencing medication choices and dietary interventions. MBP shows promise as an excellent biomarker for distinguishing true EoE from eosinophilia caused by IBD. When combined with endoscopic and histologic changes, MBP can assist with the diagnosis of EoE in IBD patients, thereby reducing the possibility of misdiagnosis.

Being diagnosed with EoE poses a challenging and life-altering experience for patients and their families. They face numerous challenges, from undergoing diagnostic procedures and treatments to adapting daily diets. Limited information is available on the eating habits of patients diagnosed with EoE. In this study, Dr Kennedy and colleagues explored how a diagnosis of EoE affects eating behaviors among pediatric patients.

The researchers conducted a prospective study involving 27 patients diagnosed with EoE and compared their eating behaviors to those of 25 healthy control participants. The participants were evaluated on the basis of their responses to four food textures (puree, soft solid, chewable, and hard solid), focusing on the number of chews per bite, sips of fluid per food, and consumption time.

The study found that, on average, patients with EoE (63.5% boys, mean age 11 years) required more chews per bite across several food textures (soft solid P = .031; chewable P = .047; and hard solid P = .037) and demonstrated increased consumption time for soft solid (P = .002), chewable (P = .005), and hard solid foods (P = .034) compared to healthy controls. In addition, endoscopic reference scores positively correlated with consumption time (r = 0.53; P = .008) and the number of chews (r = 0.45; P = .027) for chewable foods as well as with the number of chews (r = 0.44; P = .043) for hard solid foods. Increased consumption time also correlated with increased eosinophil counts (r = 0.42; P = .050) and decreased esophageal distensibility (r = -0.82; P < .0001).

Though these findings open promising avenues for the noninvasive assessment and personalized management of EoE, further research with larger, longitudinal studies is essential to validate these behaviors as reliable clinical biomarkers. Increasing the sample size would enhance the study's power and broaden the generalizability of its findings to a wider pediatric EoE population. The study's cross-sectional nature limits the ability to assess how eating behaviors change over time with treatment or disease progression.

This study underscores the potential of eating behaviors as clinical markers for pediatric patients with EoE, enabling early identification through increased chewing and consumption times, especially with harder textures. Such markers could prompt diagnostic evaluations in settings where endoscopy and biopsy are gold standards for diagnosing EoE. Moreover, eating patterns could assist in monitoring disease activity and progression, offering a noninvasive means of assessing disease status and response to therapy, thus allowing for more frequent assessments of disease status without the need for invasive procedures. Understanding these behaviors allows healthcare providers to tailor dietary advice and interventions, potentially enhancing treatment compliance and improving the quality of life for pediatric patients with EoE.

This study provides compelling evidence that a twice-daily dosing regimen of moderate-dose proton pump inhibitors (PPIs) is superior to a once-daily regimen for inducing histologic remission in eosinophilic esophagitis (EoE). This finding suggests a significant paradigm shift in EoE management, challenging the current standard treatment guideline that recommends a PPI trial of 20-40 mg twice daily. The limited data on various dosing regimens for EoE treatment underscores the importance of this research. Dr Muftah and colleagues from Brigham and Women's Hospital have conducted a novel retrospective cohort study to address the question: Does a twice-daily PPI dose induce a higher remission rate in EoE than a once-daily regimen does regardless of the total daily dose?

The study enrolled adult patients with newly-diagnosed treatment-naive EoE at a tertiary care center, dividing participants into four groups on the basis of their treatment regimen: once-daily standard dose (20 mg omeprazole), once-daily moderate dose (40 mg), twice-daily moderate dose (20 mg), and twice-daily high dose (40 mg). Patients underwent endoscopy 8-12 weeks after initiating PPI treatment, with the primary outcome being the histologic response to PPI, defined as fewer than 15 eosinophils/high power field in repeat esophageal biopsies.

Out of 305 patients (54.6% men, mean age 44.7 ± 16.7 years), 42.3% achieved a histologic response to PPI treatment. Patients receiving the standard PPI dose (20 mg omeprazole once daily) vs those on twice-daily moderate and high doses showed significantly higher histologic response rates (52.8% vs 11.8%, P < .0001; and 54.3% vs 11.8%, P < .0001; respectively). Multivariable analysis revealed that twice-daily moderate and high doses were significantly more effective (adjusted odds ration [aOR] 6.75; CI 2.53-18.0, P = .0008; and aOR 12.8, CI 4.69-34.8, P < .001; respectively).

However, the study's retrospective design limits its ability to establish causality and may introduce selection bias. In addition, the lack of specified adjustments for PPI dosing based on diet and lifestyle factors across the cohort could influence treatment response and outcomes. Last, as a single-center study, the results may not generalize across diverse patient populations, particularly those with different demographics or disease severities.

This research heralds a shift toward a more effective treatment strategy in EoE management, suggesting that a twice-daily PPI regimen may be more beneficial than once-daily dosing is for inducing histologic remission, especially in patients inadequately responding to once-daily PPI treatment. It advocates for a personalized treatment approach, considering factors such as symptom severity, previous PPI response, and potential for adherence to a twice-daily regimen.

Distinguishing between inflammatory bowel disease (IBD)–induced eosinophilia and EoE poses a significant challenge for clinicians. Given that the incidence of EoE is 3-5 times higher in patients with IBD compared with the general population, there is a pressing need for new biomarkers to differentiate between these two conditions. In response to this need, Dr Butzke and colleagues at Nemours Children's Health in Wilmington, Delaware, conducted a retrospective study to evaluate the roles of Major Basic Protein (MBP) and interleukin (IL)-13 in distinguishing these diseases. The study included participants who underwent esophagogastroduodenoscopy with esophageal biopsies for IBD workup or suspicion of EoE. It comprised 27 patients with EoE-IBD, 39 with EoE, 29 with IBD eosinophilia, 30 with IBD only, and 30 control patients. The biopsies were stained with MBP and IL-13 antibodies, and the results (percent staining/total tissue area), demographic, and clinical findings were compared among the groups.

The study revealed that MBP staining levels among patients with EoE-IBD were 3.8 units, which is significantly lower than those in the EoE group at 52.8 units and higher than those with IBD eosinophilia at 0.2 units (P < .001). IL-13 expression was significantly higher only compared with the IBD and control groups and not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity, whereas IL-13 demonstrated 83% sensitivity and 90% specificity using a cutoff point from the cohort of patients without EoE-IBD. Based on the MBP cutoff point of 3.49 units that distinguished between EoE and non-EoE cases, 100% of patients with EoE were MBP-positive compared with 3% of patients with IBD-associated eosinophilia (P < .05).

To implement this new biomarker into clinical practice, guidelines for interpreting MBP staining results should be developed and established, including defining cutoff points for positive and negative results. However, this study faces several limitations, such as not evaluating the differences in MBP results based on EoE-IBD type and disease activity. The retrospective nature of the study and its small sample size limit its power. In addition, the study did not assess how different treatments and disease activity affect MBP levels nor did it address the lack of longitudinal evaluation in assessing MBP levels.

Despite these limitations, the study presents a compelling case for the use of MBP as a biomarker to distinguish true EoE from EoE-IBD. This differentiation is crucial because it can guide therapeutic approaches, influencing medication choices and dietary interventions. MBP shows promise as an excellent biomarker for distinguishing true EoE from eosinophilia caused by IBD. When combined with endoscopic and histologic changes, MBP can assist with the diagnosis of EoE in IBD patients, thereby reducing the possibility of misdiagnosis.

Being diagnosed with EoE poses a challenging and life-altering experience for patients and their families. They face numerous challenges, from undergoing diagnostic procedures and treatments to adapting daily diets. Limited information is available on the eating habits of patients diagnosed with EoE. In this study, Dr Kennedy and colleagues explored how a diagnosis of EoE affects eating behaviors among pediatric patients.

The researchers conducted a prospective study involving 27 patients diagnosed with EoE and compared their eating behaviors to those of 25 healthy control participants. The participants were evaluated on the basis of their responses to four food textures (puree, soft solid, chewable, and hard solid), focusing on the number of chews per bite, sips of fluid per food, and consumption time.

The study found that, on average, patients with EoE (63.5% boys, mean age 11 years) required more chews per bite across several food textures (soft solid P = .031; chewable P = .047; and hard solid P = .037) and demonstrated increased consumption time for soft solid (P = .002), chewable (P = .005), and hard solid foods (P = .034) compared to healthy controls. In addition, endoscopic reference scores positively correlated with consumption time (r = 0.53; P = .008) and the number of chews (r = 0.45; P = .027) for chewable foods as well as with the number of chews (r = 0.44; P = .043) for hard solid foods. Increased consumption time also correlated with increased eosinophil counts (r = 0.42; P = .050) and decreased esophageal distensibility (r = -0.82; P < .0001).

Though these findings open promising avenues for the noninvasive assessment and personalized management of EoE, further research with larger, longitudinal studies is essential to validate these behaviors as reliable clinical biomarkers. Increasing the sample size would enhance the study's power and broaden the generalizability of its findings to a wider pediatric EoE population. The study's cross-sectional nature limits the ability to assess how eating behaviors change over time with treatment or disease progression.

This study underscores the potential of eating behaviors as clinical markers for pediatric patients with EoE, enabling early identification through increased chewing and consumption times, especially with harder textures. Such markers could prompt diagnostic evaluations in settings where endoscopy and biopsy are gold standards for diagnosing EoE. Moreover, eating patterns could assist in monitoring disease activity and progression, offering a noninvasive means of assessing disease status and response to therapy, thus allowing for more frequent assessments of disease status without the need for invasive procedures. Understanding these behaviors allows healthcare providers to tailor dietary advice and interventions, potentially enhancing treatment compliance and improving the quality of life for pediatric patients with EoE.

This study provides compelling evidence that a twice-daily dosing regimen of moderate-dose proton pump inhibitors (PPIs) is superior to a once-daily regimen for inducing histologic remission in eosinophilic esophagitis (EoE). This finding suggests a significant paradigm shift in EoE management, challenging the current standard treatment guideline that recommends a PPI trial of 20-40 mg twice daily. The limited data on various dosing regimens for EoE treatment underscores the importance of this research. Dr Muftah and colleagues from Brigham and Women's Hospital have conducted a novel retrospective cohort study to address the question: Does a twice-daily PPI dose induce a higher remission rate in EoE than a once-daily regimen does regardless of the total daily dose?

The study enrolled adult patients with newly-diagnosed treatment-naive EoE at a tertiary care center, dividing participants into four groups on the basis of their treatment regimen: once-daily standard dose (20 mg omeprazole), once-daily moderate dose (40 mg), twice-daily moderate dose (20 mg), and twice-daily high dose (40 mg). Patients underwent endoscopy 8-12 weeks after initiating PPI treatment, with the primary outcome being the histologic response to PPI, defined as fewer than 15 eosinophils/high power field in repeat esophageal biopsies.

Out of 305 patients (54.6% men, mean age 44.7 ± 16.7 years), 42.3% achieved a histologic response to PPI treatment. Patients receiving the standard PPI dose (20 mg omeprazole once daily) vs those on twice-daily moderate and high doses showed significantly higher histologic response rates (52.8% vs 11.8%, P < .0001; and 54.3% vs 11.8%, P < .0001; respectively). Multivariable analysis revealed that twice-daily moderate and high doses were significantly more effective (adjusted odds ration [aOR] 6.75; CI 2.53-18.0, P = .0008; and aOR 12.8, CI 4.69-34.8, P < .001; respectively).

However, the study's retrospective design limits its ability to establish causality and may introduce selection bias. In addition, the lack of specified adjustments for PPI dosing based on diet and lifestyle factors across the cohort could influence treatment response and outcomes. Last, as a single-center study, the results may not generalize across diverse patient populations, particularly those with different demographics or disease severities.

This research heralds a shift toward a more effective treatment strategy in EoE management, suggesting that a twice-daily PPI regimen may be more beneficial than once-daily dosing is for inducing histologic remission, especially in patients inadequately responding to once-daily PPI treatment. It advocates for a personalized treatment approach, considering factors such as symptom severity, previous PPI response, and potential for adherence to a twice-daily regimen.

Distinguishing between inflammatory bowel disease (IBD)–induced eosinophilia and EoE poses a significant challenge for clinicians. Given that the incidence of EoE is 3-5 times higher in patients with IBD compared with the general population, there is a pressing need for new biomarkers to differentiate between these two conditions. In response to this need, Dr Butzke and colleagues at Nemours Children's Health in Wilmington, Delaware, conducted a retrospective study to evaluate the roles of Major Basic Protein (MBP) and interleukin (IL)-13 in distinguishing these diseases. The study included participants who underwent esophagogastroduodenoscopy with esophageal biopsies for IBD workup or suspicion of EoE. It comprised 27 patients with EoE-IBD, 39 with EoE, 29 with IBD eosinophilia, 30 with IBD only, and 30 control patients. The biopsies were stained with MBP and IL-13 antibodies, and the results (percent staining/total tissue area), demographic, and clinical findings were compared among the groups.

The study revealed that MBP staining levels among patients with EoE-IBD were 3.8 units, which is significantly lower than those in the EoE group at 52.8 units and higher than those with IBD eosinophilia at 0.2 units (P < .001). IL-13 expression was significantly higher only compared with the IBD and control groups and not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity, whereas IL-13 demonstrated 83% sensitivity and 90% specificity using a cutoff point from the cohort of patients without EoE-IBD. Based on the MBP cutoff point of 3.49 units that distinguished between EoE and non-EoE cases, 100% of patients with EoE were MBP-positive compared with 3% of patients with IBD-associated eosinophilia (P < .05).

To implement this new biomarker into clinical practice, guidelines for interpreting MBP staining results should be developed and established, including defining cutoff points for positive and negative results. However, this study faces several limitations, such as not evaluating the differences in MBP results based on EoE-IBD type and disease activity. The retrospective nature of the study and its small sample size limit its power. In addition, the study did not assess how different treatments and disease activity affect MBP levels nor did it address the lack of longitudinal evaluation in assessing MBP levels.

Despite these limitations, the study presents a compelling case for the use of MBP as a biomarker to distinguish true EoE from EoE-IBD. This differentiation is crucial because it can guide therapeutic approaches, influencing medication choices and dietary interventions. MBP shows promise as an excellent biomarker for distinguishing true EoE from eosinophilia caused by IBD. When combined with endoscopic and histologic changes, MBP can assist with the diagnosis of EoE in IBD patients, thereby reducing the possibility of misdiagnosis.

Being diagnosed with EoE poses a challenging and life-altering experience for patients and their families. They face numerous challenges, from undergoing diagnostic procedures and treatments to adapting daily diets. Limited information is available on the eating habits of patients diagnosed with EoE. In this study, Dr Kennedy and colleagues explored how a diagnosis of EoE affects eating behaviors among pediatric patients.

The researchers conducted a prospective study involving 27 patients diagnosed with EoE and compared their eating behaviors to those of 25 healthy control participants. The participants were evaluated on the basis of their responses to four food textures (puree, soft solid, chewable, and hard solid), focusing on the number of chews per bite, sips of fluid per food, and consumption time.

The study found that, on average, patients with EoE (63.5% boys, mean age 11 years) required more chews per bite across several food textures (soft solid P = .031; chewable P = .047; and hard solid P = .037) and demonstrated increased consumption time for soft solid (P = .002), chewable (P = .005), and hard solid foods (P = .034) compared to healthy controls. In addition, endoscopic reference scores positively correlated with consumption time (r = 0.53; P = .008) and the number of chews (r = 0.45; P = .027) for chewable foods as well as with the number of chews (r = 0.44; P = .043) for hard solid foods. Increased consumption time also correlated with increased eosinophil counts (r = 0.42; P = .050) and decreased esophageal distensibility (r = -0.82; P < .0001).

Though these findings open promising avenues for the noninvasive assessment and personalized management of EoE, further research with larger, longitudinal studies is essential to validate these behaviors as reliable clinical biomarkers. Increasing the sample size would enhance the study's power and broaden the generalizability of its findings to a wider pediatric EoE population. The study's cross-sectional nature limits the ability to assess how eating behaviors change over time with treatment or disease progression.

This study underscores the potential of eating behaviors as clinical markers for pediatric patients with EoE, enabling early identification through increased chewing and consumption times, especially with harder textures. Such markers could prompt diagnostic evaluations in settings where endoscopy and biopsy are gold standards for diagnosing EoE. Moreover, eating patterns could assist in monitoring disease activity and progression, offering a noninvasive means of assessing disease status and response to therapy, thus allowing for more frequent assessments of disease status without the need for invasive procedures. Understanding these behaviors allows healthcare providers to tailor dietary advice and interventions, potentially enhancing treatment compliance and improving the quality of life for pediatric patients with EoE.

TOPLINE:

Doxorubicin increases the risk for breast cancer in women with Hodgkin lymphoma, suggesting the need for increased surveillance.

METHODOLOGY:

• Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
• Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
• To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
• Patients had survived for at least 5 years, and 57% received doxorubicin.

TAKEAWAY:

• Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
• The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
• The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
• After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.

IN PRACTICE:

The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.

SOURCE:

The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology. 

LIMITATIONS:

Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.

DISCLOSURES:

The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Doxorubicin increases the risk for breast cancer in women with Hodgkin lymphoma, suggesting the need for increased surveillance.

METHODOLOGY:

• Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
• Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
• To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
• Patients had survived for at least 5 years, and 57% received doxorubicin.

TAKEAWAY:

• Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
• The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
• The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
• After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.

IN PRACTICE:

The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.

SOURCE:

The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology. 

LIMITATIONS:

Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.

DISCLOSURES:

The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Doxorubicin increases the risk for breast cancer in women with Hodgkin lymphoma, suggesting the need for increased surveillance.

METHODOLOGY:

• Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
• Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
• To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
• Patients had survived for at least 5 years, and 57% received doxorubicin.

TAKEAWAY:

• Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
• The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
• The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
• After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.

IN PRACTICE:

The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.

SOURCE:

The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology. 

LIMITATIONS:

Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.

DISCLOSURES:

The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
 

A version of this article appeared on Medscape.com.

Will the new US Department of Veterans Affairs (VA) pharmacy software be safe and effective? That was the topic when David Case, the VA Deputy Inspector General, spoke in the US House of Representatives Veterans Affairs Committee technology modernization subcommittee hearing on February 15.

Questions like that have dogged the project since 2018, when the VA began rolling out the Oracle Cerner electronic health record (EHR) system as the successor to ViSTA.

The Oracle system has been beset by one glitch after another since its arrival. And in that time, Case said, the VA Office of Inspector General (OIG) has been engaging with VA employees at sites in Washington, Oregon, Ohio, Illinois, and other locations where the modernization program has been piloted.

The most recent OIG investigation of pharmacy-related patient safety issues began with a review of an allegation of a prescription backlog at Columbus, Ohio, where the system went live on April 30, 2022. The OIG found that facility leaders took “timely and sustainable steps” to manage that issue. However, other unresolved patient safety issues came to light, such as medication inaccuracies, inaccurate medication data, and insufficient staffing. The OIG also found staff were creating “numerous work arounds” to provide patient care, and that the volume of staff educational materials for pharmacy-related functions was “overwhelming.”

Those problems were just the latest in a long queue. In May 2021, after the first VA deployment of the new EHR at the Mann-Grandstaff VA Medical Center in Spokane, Washington, a pharmacy patient safety team under the VA National Center for Patient Safety (NCPS) also had identified patient safety issues and “multiple” concerns regarding the system’s usability. For example, updates to a patient’s active medication list were not routinely reflected at the patient’s next appointment. Despite knowing about such challenges, Case noted in his report, VA leaders deployed the new EHR at 4 more VA medical centers.

Cerner/ViSTA Communication

One major cause of the current problems is the way the systems “talk” to each other. EHR information is communicated between VHA facilities through channels that include the Joint Longitudinal Viewer (JLV) and the Health Data Repository, which stores patient-specific clinical information from both the legacy and the new EHR systems. The JLV application allows clinicians to access a read only version of a patient’s EHR from both systems.

Every medication used in VHA has a VA Unique Identifier (VUID). When a patient is prescribed a medication at a new EHR site, that medication’s VUID is sent to the Health Data Repository. If that patient seeks care from a legacy health care practitioner (HCP), and that HCP enters a medication order, a software interface accesses the VUID from the Health Data Repository to verify that the medication being prescribed is safe and compatible with the medications and allergies previously documented in the patient’s record.

However, on March 31, 2023, staff from a ViSTA site found an incorrect medication order when prescribing a new medication to a patient who had received care and medications at a new EHR site. This in turn led to the discovery that an error in Oracle software coding had resulted in the “widespread transmission” of incorrect VUIDs from new EHR sites to legacy EHR sites, the OIG found. VA leaders and HCPs were notified of the potential clinical impact and were given specific instructions on how to mitigate the issue. They were asked to “please share widely.”

On top of that, days later, patient safety managers across the Veterans Health Administration (VHA) were told that drug-to-drug interactions, duplicate medication orders, and allergy checks were not functioning as expected, and they too were provided with remedial actions.

Oracle applied a successful software patch on in April 2023, to ensure accurate VUIDs were attached to all mail order pharmacy–processed prescriptions from that date forward. However, the OIG learned the incorrect VUIDs sent from new EHR sites and stored in the Health Data Repository from as far back as October 2020 had not been corrected. Case told the subcommittee that on November 29, 2023, the VHA Pharmacy Council reported withdrawing a request for Oracle to send corrected medication VUID data to the Health Data Repository, on the presumption that remaining inaccurate VUIDs would expire in early April 2024, and the data would be corrected at that time.

The OIG is concerned, Case said, that patient medication data remains inaccurate almost a year after VA learned of the issue. The mail order pharmacy-related data generated from approximately 120,000 patients served by new EHR sites are still incorrect. These patients face an ongoing risk of an adverse medication-related event if they receive care and medications from a VA medical center using the legacy EHR system.

The OIG also learned of other problems associated with transmission of medication and allergy information, which could have consequences such as:

• Patient medications being discontinued or stopped by new HCPs using Cerner that appear in ViSTA as active and current prescriptions;
• Allergy-warning messages not appearing when intended or inappropriately appearing for the wrong medication;
• Duplicate medication order checks not appearing when intended or inappropriately appearing for the wrong drug;
• Patient active medication lists having incomplete or inaccurate information, such as missing prescriptions, duplicate prescriptions, or incorrect medication order statuses.

The OIG warned VHA employees about the risks, although it wasn’t possible to determine who might actually be at risk. A VHA leader told the OIG that all patients who have been prescribed any medications or have medication allergies documented at a at a Cerner site are at risk. That could mean as many as 250,000 patients: As of September 2023, approximately 190,000 patients had a medication prescribed and 126,000 had an allergy documented at a new EHR site.

Case Example

Not surprisingly, “the OIG is not confident in [EHRM-Integration Office] leaders’ oversight and control of the new systems’ Health Data Repository interface programming,” Case said. He cited the case of a patient with posttraumatic stress disorder and traumatic brain injury with adrenal insufficiency. Four days prior to admission, a ViSTA site pharmacist used the EHR to perform a medication reconciliation for the patient. The data available did not include the patient’s most recent prednisone prescription, which had been ordered by an HCP at a facility using Cerner.

A nurse practitioner performed another reconciliation when the patient was admitted to the residential program, but the patient was unsure of all their medications. Because the most recent prednisone prescription was not visible in ViSTA, the prednisone appeared to have been completed at least 3 months prior to admission and was therefore not prescribed in the admission medication orders.

Five days into the residential program, the patient began exhibiting unusual behaviors associated with the lack of prednisone. The patient realized they needed more prednisone, but the nurse explained there was no prednisone on the patient’s medication list. Eventually, the patient found the active prednisone order on their personal cell phone and was transferred to a local emergency department for care.

Work Arounds

The VHA’s efforts to forestall or mitigate system errors have in some cases had a cascade effect. For example, HCPs must essentially back up what the automated software is intended to do, with “complex, time-consuming” multistep manual safety checks when prescribing new medications for patients previously cared for at a Cerner site. The OIG is concerned that this increased vigilance is “unsustainable” by pharmacists and frontline staff and could lead to burnout and medication-related patient safety events. After the new EHR launched, the OIG found, burnout symptoms for pharmacy staff increased. Nonetheless, Case told the committee, OIG staff “have observed [employees’] unwavering commitment to prioritizing the care of patients while mitigating implementation challenges.”

EHR-related workload burdens have necessitated other adjustments. Columbus, for instance, hired 9 full-time clinical pharmacists—a 62% staffing increase—to help reduce the backlog. Pharmacy leaders created approximately 29 additional work-arounds to support pharmacy staff and prevent delays. Facility pharmacy leaders also developed approximately 25 educational materials, such as tip sheets, reference guides, and job aids. The OIG’s concern—apart from the overwhelming amount of information for staff to implement—is that such prophylactic measures may in fact give rise to inconsistent practices, which increase risks to patient safety.

Committed to Working With the VA

Mike Sicilia, executive vice president of Oracle Corporation, told lawmakers in the hearing, “After the initial deployments, it became clear that the pharmacy system needed to be enhanced to better meet VA’s needs. To that end, in August 2022, shortly after Oracle completed its acquisition of Cerner, VA contracted with us for seven enhancements that overall would adapt the pharmacy system to a more bidirectional system between VA providers placing prescription orders and VA pharmacists fulfilling and dispensing them.” Those enhancements are all live for VA providers and pharmacists to use now, he said, except for one that is undergoing additional testing.

He added, “As with any healthcare technology system, there is a need for continuous improvements but that does not mean the system is not safe and effective in its current state. Oracle is committed to working with VA … throughout the reset period to identify workflows and other items that can be simplified or streamlined to improve the overall user and pharmacy experience.”

Standardizing workflows and ensuring training and communications to pharmacists about the latest updates will discourage use of work-arounds, Sicilia said, and “help with improving morale and satisfaction with the system.” During a visit in early February by VA and the Oracle team to the Lovell Federal Health Care Center in North Chicago, “feedback from pharmacists was positive about the training and readiness for using the new pharmacy system.”

The backlog, at least, may be resolved. Sicilia said on average more than 215,000 outpatient prescriptions are being filled each month. “The current live sites do not have a backlog in filling prescriptions. Recent data from this month show that three of the five live sites have zero prescriptions waiting to be processed that are older than seven days. The two other live sites have an average of two prescriptions older than seven days,” he said.

Although Oracle Health has since resolved some of the identified issues, the OIG is concerned that the new EHR will continue to be deployed at medical facilities despite “myriad” as-yet unresolved issues related to inaccurate medication ordering, reconciliation, and dispensing. The VHA has paused Cerner deployments multiple times.

“It is unclear whether identified problems are being adequately resolved before additional deployments,” Case said. “There is also the question of whether there is sufficient transparency and communication among EHRM-IO, VHA and facility leaders, VA leaders, and Oracle Health needed for quality control and critical coordination. Trust in VA is also dependent on patients being fully and quickly advised when issues affecting them are identified and addressed. As VA moves toward its deployment next month at a complex facility jointly operated with the Department of Defense, transparency, communication, and program management will be essential to getting it right. Failures in these areas risk cascading problems.”

Will the new US Department of Veterans Affairs (VA) pharmacy software be safe and effective? That was the topic when David Case, the VA Deputy Inspector General, spoke in the US House of Representatives Veterans Affairs Committee technology modernization subcommittee hearing on February 15.

Questions like that have dogged the project since 2018, when the VA began rolling out the Oracle Cerner electronic health record (EHR) system as the successor to ViSTA.

The Oracle system has been beset by one glitch after another since its arrival. And in that time, Case said, the VA Office of Inspector General (OIG) has been engaging with VA employees at sites in Washington, Oregon, Ohio, Illinois, and other locations where the modernization program has been piloted.

The most recent OIG investigation of pharmacy-related patient safety issues began with a review of an allegation of a prescription backlog at Columbus, Ohio, where the system went live on April 30, 2022. The OIG found that facility leaders took “timely and sustainable steps” to manage that issue. However, other unresolved patient safety issues came to light, such as medication inaccuracies, inaccurate medication data, and insufficient staffing. The OIG also found staff were creating “numerous work arounds” to provide patient care, and that the volume of staff educational materials for pharmacy-related functions was “overwhelming.”

Those problems were just the latest in a long queue. In May 2021, after the first VA deployment of the new EHR at the Mann-Grandstaff VA Medical Center in Spokane, Washington, a pharmacy patient safety team under the VA National Center for Patient Safety (NCPS) also had identified patient safety issues and “multiple” concerns regarding the system’s usability. For example, updates to a patient’s active medication list were not routinely reflected at the patient’s next appointment. Despite knowing about such challenges, Case noted in his report, VA leaders deployed the new EHR at 4 more VA medical centers.

Cerner/ViSTA Communication

One major cause of the current problems is the way the systems “talk” to each other. EHR information is communicated between VHA facilities through channels that include the Joint Longitudinal Viewer (JLV) and the Health Data Repository, which stores patient-specific clinical information from both the legacy and the new EHR systems. The JLV application allows clinicians to access a read only version of a patient’s EHR from both systems.

Every medication used in VHA has a VA Unique Identifier (VUID). When a patient is prescribed a medication at a new EHR site, that medication’s VUID is sent to the Health Data Repository. If that patient seeks care from a legacy health care practitioner (HCP), and that HCP enters a medication order, a software interface accesses the VUID from the Health Data Repository to verify that the medication being prescribed is safe and compatible with the medications and allergies previously documented in the patient’s record.

However, on March 31, 2023, staff from a ViSTA site found an incorrect medication order when prescribing a new medication to a patient who had received care and medications at a new EHR site. This in turn led to the discovery that an error in Oracle software coding had resulted in the “widespread transmission” of incorrect VUIDs from new EHR sites to legacy EHR sites, the OIG found. VA leaders and HCPs were notified of the potential clinical impact and were given specific instructions on how to mitigate the issue. They were asked to “please share widely.”

On top of that, days later, patient safety managers across the Veterans Health Administration (VHA) were told that drug-to-drug interactions, duplicate medication orders, and allergy checks were not functioning as expected, and they too were provided with remedial actions.

Oracle applied a successful software patch on in April 2023, to ensure accurate VUIDs were attached to all mail order pharmacy–processed prescriptions from that date forward. However, the OIG learned the incorrect VUIDs sent from new EHR sites and stored in the Health Data Repository from as far back as October 2020 had not been corrected. Case told the subcommittee that on November 29, 2023, the VHA Pharmacy Council reported withdrawing a request for Oracle to send corrected medication VUID data to the Health Data Repository, on the presumption that remaining inaccurate VUIDs would expire in early April 2024, and the data would be corrected at that time.

The OIG is concerned, Case said, that patient medication data remains inaccurate almost a year after VA learned of the issue. The mail order pharmacy-related data generated from approximately 120,000 patients served by new EHR sites are still incorrect. These patients face an ongoing risk of an adverse medication-related event if they receive care and medications from a VA medical center using the legacy EHR system.

The OIG also learned of other problems associated with transmission of medication and allergy information, which could have consequences such as:

• Patient medications being discontinued or stopped by new HCPs using Cerner that appear in ViSTA as active and current prescriptions;
• Allergy-warning messages not appearing when intended or inappropriately appearing for the wrong medication;
• Duplicate medication order checks not appearing when intended or inappropriately appearing for the wrong drug;
• Patient active medication lists having incomplete or inaccurate information, such as missing prescriptions, duplicate prescriptions, or incorrect medication order statuses.

The OIG warned VHA employees about the risks, although it wasn’t possible to determine who might actually be at risk. A VHA leader told the OIG that all patients who have been prescribed any medications or have medication allergies documented at a at a Cerner site are at risk. That could mean as many as 250,000 patients: As of September 2023, approximately 190,000 patients had a medication prescribed and 126,000 had an allergy documented at a new EHR site.

Case Example

Not surprisingly, “the OIG is not confident in [EHRM-Integration Office] leaders’ oversight and control of the new systems’ Health Data Repository interface programming,” Case said. He cited the case of a patient with posttraumatic stress disorder and traumatic brain injury with adrenal insufficiency. Four days prior to admission, a ViSTA site pharmacist used the EHR to perform a medication reconciliation for the patient. The data available did not include the patient’s most recent prednisone prescription, which had been ordered by an HCP at a facility using Cerner.

A nurse practitioner performed another reconciliation when the patient was admitted to the residential program, but the patient was unsure of all their medications. Because the most recent prednisone prescription was not visible in ViSTA, the prednisone appeared to have been completed at least 3 months prior to admission and was therefore not prescribed in the admission medication orders.

Five days into the residential program, the patient began exhibiting unusual behaviors associated with the lack of prednisone. The patient realized they needed more prednisone, but the nurse explained there was no prednisone on the patient’s medication list. Eventually, the patient found the active prednisone order on their personal cell phone and was transferred to a local emergency department for care.

Work Arounds

The VHA’s efforts to forestall or mitigate system errors have in some cases had a cascade effect. For example, HCPs must essentially back up what the automated software is intended to do, with “complex, time-consuming” multistep manual safety checks when prescribing new medications for patients previously cared for at a Cerner site. The OIG is concerned that this increased vigilance is “unsustainable” by pharmacists and frontline staff and could lead to burnout and medication-related patient safety events. After the new EHR launched, the OIG found, burnout symptoms for pharmacy staff increased. Nonetheless, Case told the committee, OIG staff “have observed [employees’] unwavering commitment to prioritizing the care of patients while mitigating implementation challenges.”

EHR-related workload burdens have necessitated other adjustments. Columbus, for instance, hired 9 full-time clinical pharmacists—a 62% staffing increase—to help reduce the backlog. Pharmacy leaders created approximately 29 additional work-arounds to support pharmacy staff and prevent delays. Facility pharmacy leaders also developed approximately 25 educational materials, such as tip sheets, reference guides, and job aids. The OIG’s concern—apart from the overwhelming amount of information for staff to implement—is that such prophylactic measures may in fact give rise to inconsistent practices, which increase risks to patient safety.

Committed to Working With the VA

Mike Sicilia, executive vice president of Oracle Corporation, told lawmakers in the hearing, “After the initial deployments, it became clear that the pharmacy system needed to be enhanced to better meet VA’s needs. To that end, in August 2022, shortly after Oracle completed its acquisition of Cerner, VA contracted with us for seven enhancements that overall would adapt the pharmacy system to a more bidirectional system between VA providers placing prescription orders and VA pharmacists fulfilling and dispensing them.” Those enhancements are all live for VA providers and pharmacists to use now, he said, except for one that is undergoing additional testing.

He added, “As with any healthcare technology system, there is a need for continuous improvements but that does not mean the system is not safe and effective in its current state. Oracle is committed to working with VA … throughout the reset period to identify workflows and other items that can be simplified or streamlined to improve the overall user and pharmacy experience.”

Standardizing workflows and ensuring training and communications to pharmacists about the latest updates will discourage use of work-arounds, Sicilia said, and “help with improving morale and satisfaction with the system.” During a visit in early February by VA and the Oracle team to the Lovell Federal Health Care Center in North Chicago, “feedback from pharmacists was positive about the training and readiness for using the new pharmacy system.”

The backlog, at least, may be resolved. Sicilia said on average more than 215,000 outpatient prescriptions are being filled each month. “The current live sites do not have a backlog in filling prescriptions. Recent data from this month show that three of the five live sites have zero prescriptions waiting to be processed that are older than seven days. The two other live sites have an average of two prescriptions older than seven days,” he said.

Although Oracle Health has since resolved some of the identified issues, the OIG is concerned that the new EHR will continue to be deployed at medical facilities despite “myriad” as-yet unresolved issues related to inaccurate medication ordering, reconciliation, and dispensing. The VHA has paused Cerner deployments multiple times.

“It is unclear whether identified problems are being adequately resolved before additional deployments,” Case said. “There is also the question of whether there is sufficient transparency and communication among EHRM-IO, VHA and facility leaders, VA leaders, and Oracle Health needed for quality control and critical coordination. Trust in VA is also dependent on patients being fully and quickly advised when issues affecting them are identified and addressed. As VA moves toward its deployment next month at a complex facility jointly operated with the Department of Defense, transparency, communication, and program management will be essential to getting it right. Failures in these areas risk cascading problems.”

Will the new US Department of Veterans Affairs (VA) pharmacy software be safe and effective? That was the topic when David Case, the VA Deputy Inspector General, spoke in the US House of Representatives Veterans Affairs Committee technology modernization subcommittee hearing on February 15.

Questions like that have dogged the project since 2018, when the VA began rolling out the Oracle Cerner electronic health record (EHR) system as the successor to ViSTA.

The Oracle system has been beset by one glitch after another since its arrival. And in that time, Case said, the VA Office of Inspector General (OIG) has been engaging with VA employees at sites in Washington, Oregon, Ohio, Illinois, and other locations where the modernization program has been piloted.

The most recent OIG investigation of pharmacy-related patient safety issues began with a review of an allegation of a prescription backlog at Columbus, Ohio, where the system went live on April 30, 2022. The OIG found that facility leaders took “timely and sustainable steps” to manage that issue. However, other unresolved patient safety issues came to light, such as medication inaccuracies, inaccurate medication data, and insufficient staffing. The OIG also found staff were creating “numerous work arounds” to provide patient care, and that the volume of staff educational materials for pharmacy-related functions was “overwhelming.”

Those problems were just the latest in a long queue. In May 2021, after the first VA deployment of the new EHR at the Mann-Grandstaff VA Medical Center in Spokane, Washington, a pharmacy patient safety team under the VA National Center for Patient Safety (NCPS) also had identified patient safety issues and “multiple” concerns regarding the system’s usability. For example, updates to a patient’s active medication list were not routinely reflected at the patient’s next appointment. Despite knowing about such challenges, Case noted in his report, VA leaders deployed the new EHR at 4 more VA medical centers.

Cerner/ViSTA Communication

One major cause of the current problems is the way the systems “talk” to each other. EHR information is communicated between VHA facilities through channels that include the Joint Longitudinal Viewer (JLV) and the Health Data Repository, which stores patient-specific clinical information from both the legacy and the new EHR systems. The JLV application allows clinicians to access a read only version of a patient’s EHR from both systems.

Every medication used in VHA has a VA Unique Identifier (VUID). When a patient is prescribed a medication at a new EHR site, that medication’s VUID is sent to the Health Data Repository. If that patient seeks care from a legacy health care practitioner (HCP), and that HCP enters a medication order, a software interface accesses the VUID from the Health Data Repository to verify that the medication being prescribed is safe and compatible with the medications and allergies previously documented in the patient’s record.

However, on March 31, 2023, staff from a ViSTA site found an incorrect medication order when prescribing a new medication to a patient who had received care and medications at a new EHR site. This in turn led to the discovery that an error in Oracle software coding had resulted in the “widespread transmission” of incorrect VUIDs from new EHR sites to legacy EHR sites, the OIG found. VA leaders and HCPs were notified of the potential clinical impact and were given specific instructions on how to mitigate the issue. They were asked to “please share widely.”

On top of that, days later, patient safety managers across the Veterans Health Administration (VHA) were told that drug-to-drug interactions, duplicate medication orders, and allergy checks were not functioning as expected, and they too were provided with remedial actions.

Oracle applied a successful software patch on in April 2023, to ensure accurate VUIDs were attached to all mail order pharmacy–processed prescriptions from that date forward. However, the OIG learned the incorrect VUIDs sent from new EHR sites and stored in the Health Data Repository from as far back as October 2020 had not been corrected. Case told the subcommittee that on November 29, 2023, the VHA Pharmacy Council reported withdrawing a request for Oracle to send corrected medication VUID data to the Health Data Repository, on the presumption that remaining inaccurate VUIDs would expire in early April 2024, and the data would be corrected at that time.

The OIG is concerned, Case said, that patient medication data remains inaccurate almost a year after VA learned of the issue. The mail order pharmacy-related data generated from approximately 120,000 patients served by new EHR sites are still incorrect. These patients face an ongoing risk of an adverse medication-related event if they receive care and medications from a VA medical center using the legacy EHR system.

The OIG also learned of other problems associated with transmission of medication and allergy information, which could have consequences such as:

• Patient medications being discontinued or stopped by new HCPs using Cerner that appear in ViSTA as active and current prescriptions;
• Allergy-warning messages not appearing when intended or inappropriately appearing for the wrong medication;
• Duplicate medication order checks not appearing when intended or inappropriately appearing for the wrong drug;
• Patient active medication lists having incomplete or inaccurate information, such as missing prescriptions, duplicate prescriptions, or incorrect medication order statuses.

The OIG warned VHA employees about the risks, although it wasn’t possible to determine who might actually be at risk. A VHA leader told the OIG that all patients who have been prescribed any medications or have medication allergies documented at a at a Cerner site are at risk. That could mean as many as 250,000 patients: As of September 2023, approximately 190,000 patients had a medication prescribed and 126,000 had an allergy documented at a new EHR site.

Case Example

Not surprisingly, “the OIG is not confident in [EHRM-Integration Office] leaders’ oversight and control of the new systems’ Health Data Repository interface programming,” Case said. He cited the case of a patient with posttraumatic stress disorder and traumatic brain injury with adrenal insufficiency. Four days prior to admission, a ViSTA site pharmacist used the EHR to perform a medication reconciliation for the patient. The data available did not include the patient’s most recent prednisone prescription, which had been ordered by an HCP at a facility using Cerner.

A nurse practitioner performed another reconciliation when the patient was admitted to the residential program, but the patient was unsure of all their medications. Because the most recent prednisone prescription was not visible in ViSTA, the prednisone appeared to have been completed at least 3 months prior to admission and was therefore not prescribed in the admission medication orders.

Five days into the residential program, the patient began exhibiting unusual behaviors associated with the lack of prednisone. The patient realized they needed more prednisone, but the nurse explained there was no prednisone on the patient’s medication list. Eventually, the patient found the active prednisone order on their personal cell phone and was transferred to a local emergency department for care.

Work Arounds

The VHA’s efforts to forestall or mitigate system errors have in some cases had a cascade effect. For example, HCPs must essentially back up what the automated software is intended to do, with “complex, time-consuming” multistep manual safety checks when prescribing new medications for patients previously cared for at a Cerner site. The OIG is concerned that this increased vigilance is “unsustainable” by pharmacists and frontline staff and could lead to burnout and medication-related patient safety events. After the new EHR launched, the OIG found, burnout symptoms for pharmacy staff increased. Nonetheless, Case told the committee, OIG staff “have observed [employees’] unwavering commitment to prioritizing the care of patients while mitigating implementation challenges.”

EHR-related workload burdens have necessitated other adjustments. Columbus, for instance, hired 9 full-time clinical pharmacists—a 62% staffing increase—to help reduce the backlog. Pharmacy leaders created approximately 29 additional work-arounds to support pharmacy staff and prevent delays. Facility pharmacy leaders also developed approximately 25 educational materials, such as tip sheets, reference guides, and job aids. The OIG’s concern—apart from the overwhelming amount of information for staff to implement—is that such prophylactic measures may in fact give rise to inconsistent practices, which increase risks to patient safety.

Committed to Working With the VA

Mike Sicilia, executive vice president of Oracle Corporation, told lawmakers in the hearing, “After the initial deployments, it became clear that the pharmacy system needed to be enhanced to better meet VA’s needs. To that end, in August 2022, shortly after Oracle completed its acquisition of Cerner, VA contracted with us for seven enhancements that overall would adapt the pharmacy system to a more bidirectional system between VA providers placing prescription orders and VA pharmacists fulfilling and dispensing them.” Those enhancements are all live for VA providers and pharmacists to use now, he said, except for one that is undergoing additional testing.

He added, “As with any healthcare technology system, there is a need for continuous improvements but that does not mean the system is not safe and effective in its current state. Oracle is committed to working with VA … throughout the reset period to identify workflows and other items that can be simplified or streamlined to improve the overall user and pharmacy experience.”

Standardizing workflows and ensuring training and communications to pharmacists about the latest updates will discourage use of work-arounds, Sicilia said, and “help with improving morale and satisfaction with the system.” During a visit in early February by VA and the Oracle team to the Lovell Federal Health Care Center in North Chicago, “feedback from pharmacists was positive about the training and readiness for using the new pharmacy system.”

The backlog, at least, may be resolved. Sicilia said on average more than 215,000 outpatient prescriptions are being filled each month. “The current live sites do not have a backlog in filling prescriptions. Recent data from this month show that three of the five live sites have zero prescriptions waiting to be processed that are older than seven days. The two other live sites have an average of two prescriptions older than seven days,” he said.

Although Oracle Health has since resolved some of the identified issues, the OIG is concerned that the new EHR will continue to be deployed at medical facilities despite “myriad” as-yet unresolved issues related to inaccurate medication ordering, reconciliation, and dispensing. The VHA has paused Cerner deployments multiple times.

“It is unclear whether identified problems are being adequately resolved before additional deployments,” Case said. “There is also the question of whether there is sufficient transparency and communication among EHRM-IO, VHA and facility leaders, VA leaders, and Oracle Health needed for quality control and critical coordination. Trust in VA is also dependent on patients being fully and quickly advised when issues affecting them are identified and addressed. As VA moves toward its deployment next month at a complex facility jointly operated with the Department of Defense, transparency, communication, and program management will be essential to getting it right. Failures in these areas risk cascading problems.”

An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.

Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.

Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.

The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.

An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.

Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.

Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.

The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.

An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.

Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.

Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.

The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.

The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.^[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.^[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.^[5]

TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.^[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.^[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.

Additional References

1. Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
2. Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
3. Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
4. Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
5. Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
6. Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
7. Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source

The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.^[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.^[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.^[5]

TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.^[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.^[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.

Additional References

1. Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
2. Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
3. Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
4. Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
5. Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
6. Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
7. Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source

The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.^[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.^[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.^[5]

TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.^[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.^[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.

Additional References

1. Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
2. Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
3. Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
4. Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
5. Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
6. Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
7. Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source

People with gout are 58% more likely to develop cardiovascular disease (CVD), according to a new analysis. This increased risk was observed across 12 different cardiovascular conditions, including heart failure, arrhythmias, and valve diseases.

“These findings suggest that the organ damage associated with gout is likely to be much broader than originally thought,” Nathalie Conrad, PhD, senior author of the research and cardiovascular epidemiologist at KU Leuven, Leuven, Belgium, said in an email. This could be useful for future research on underlying biological mechanisms driving CVD risk in gout, she added.

While previous research has tied gout to increased cardiovascular risk, these studies “largely focused on coronary heart disease, stroke, and thromboembolic outcomes,” she explained, and have been smaller in size.

This new study included more than 862,000 individuals, which permitted researchers to investigate rarer CVD outcomes such as myocarditis and pericarditis.

For the study, researchers used electronic health records from the UK Clinical Practice Research Datalink, a primary care database that contains anonymized health data for about 22 million individuals. Using these data, they identified more than 152,600 individuals with gout. Patients included in the analysis were diagnosed between 2000 and 2017, younger than 80 years at diagnosis, and free of CVD for at least 12 months after their gout diagnosis.

Patients with gout were compared with nearly 710,000 controls, matched on demographic factors such as age, sex, and geographic region.

Researchers then investigated the incidence of 12 CVDs, including atherosclerotic diseases, degenerative and thromboembolic diseases, and arrythmias, between the two groups from January 1, 2000, to June 30, 2019.

The findings were published in the March 2024 issue of The Lancet Rheumatology. Overall, patients with gout were 58% more likely to develop any CVD than their matched comparators without gout. There was a higher disease incidence among patients with gout for each of the 12 conditions. This association was more pronounced in women (hazard ratio [HR], 1.88) than in men (HR, 1.49), and gout amplified the risk for CVD in younger individuals to a greater extent.

Individuals younger than 45 years with gout were more than twice as likely to develop CVD compared with similarly aged individuals without gout. For comparison, individuals aged 45-54 years with gout were 84% more likely to develop CVD, and individuals aged 55-64 years were 57% more likely to develop CVD than matched controls.

Conduction system disease had the highest incident risk (HR, 1.88), followed by heart failure and valve disease (HR, 1.85 for both).

Individuals with gout had higher rates of comorbidities than the controls, including hypertension, obesity, and dyslipidemia. Overall, CVD risk was slightly attenuated after adjustment for traditional CVD risk factors such as smoking, blood pressure, and body mass index but still significant: Patients with gout had a 31% higher risk for CVD than comparators.

This shows “that known CVD risk factors only explain part of the CVD risks seen in patients with gout,” Dr. Conrad said. Other factors such as inflammation and other disease activity factors could be at play, she explained, which would need to be explored in future research.

The study “shows the whole landscape” of CVD and gout, Michael H. Pillinger, MD, rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Grossman School of Medicine in New York City, said in an interview. He was not involved with the research.

“Every possible cardiovascular disease that they could think of was something that gout patients had more of than the non-gout patients,” he added. “I think this is going to be a paper that gets cited a lot, at minimum when describing the background of risk when we look at gout patients.”

The study had some limitations, including that researchers were unable to account for how medications such as nonsteroidal anti-inflammatory drugs, corticosteroids, colchicine, or allopurinol may have affected the association between gout and CVD.

“This is because analyses of nonrandomized treatment can be confounded by indication, wherein it is difficult to differentiate the effects of the treatment from underlying disease severity,” the authors wrote.

There was also a large amount of missing data on blood pressure, body mass index, smoking status, and other health information relevant to cardiovascular risk, so sensitivity analyses adjusting for these factors “should be interpreted with caution,” they added.

Dr. Pillinger also noted that the rates of comorbidities in the gout study population were lower than what have been found in US study populations. For example, about 40% of patients with gout in the analysis had hypertension, while other studies have suggested higher rates of 60%-70%, he said. However, it’s not clear if these differences could have affected outcomes. He added that these limitations do not “in any way weaken [the authors’] conclusion.”

The findings call for better strategies to reduce CVD risk in patients with gout, Dr. Conrad noted.

“Further improvements could come from better recognition and intervention on CVD risk factors (eg, through lifestyle changes or drug therapies where they are indicated), as well as proactive screening for heart disease in patients with gout, which could allow early diagnosis and interventions to delay more severe outcomes,” she added.

This study was funded by Research Foundation Flanders. Dr. Conrad was funded by a personal fellowship from the Research Foundation Flanders and a European Society of Cardiology research grant. She received royalties from Oxford University Innovation. Four of Dr. Conrad’s eight coauthors also reported financial relationships with pharmaceutical companies. Dr. Pillinger served as a consultant to Amgen, Federation Bio, Fortress Biotech, and Scilex, and he holds an investigator-initiated grant from Hikma.

A version of this article appeared on Medscape.com.

People with gout are 58% more likely to develop cardiovascular disease (CVD), according to a new analysis. This increased risk was observed across 12 different cardiovascular conditions, including heart failure, arrhythmias, and valve diseases.

“These findings suggest that the organ damage associated with gout is likely to be much broader than originally thought,” Nathalie Conrad, PhD, senior author of the research and cardiovascular epidemiologist at KU Leuven, Leuven, Belgium, said in an email. This could be useful for future research on underlying biological mechanisms driving CVD risk in gout, she added.

While previous research has tied gout to increased cardiovascular risk, these studies “largely focused on coronary heart disease, stroke, and thromboembolic outcomes,” she explained, and have been smaller in size.

This new study included more than 862,000 individuals, which permitted researchers to investigate rarer CVD outcomes such as myocarditis and pericarditis.

For the study, researchers used electronic health records from the UK Clinical Practice Research Datalink, a primary care database that contains anonymized health data for about 22 million individuals. Using these data, they identified more than 152,600 individuals with gout. Patients included in the analysis were diagnosed between 2000 and 2017, younger than 80 years at diagnosis, and free of CVD for at least 12 months after their gout diagnosis.

Patients with gout were compared with nearly 710,000 controls, matched on demographic factors such as age, sex, and geographic region.

Researchers then investigated the incidence of 12 CVDs, including atherosclerotic diseases, degenerative and thromboembolic diseases, and arrythmias, between the two groups from January 1, 2000, to June 30, 2019.

The findings were published in the March 2024 issue of The Lancet Rheumatology. Overall, patients with gout were 58% more likely to develop any CVD than their matched comparators without gout. There was a higher disease incidence among patients with gout for each of the 12 conditions. This association was more pronounced in women (hazard ratio [HR], 1.88) than in men (HR, 1.49), and gout amplified the risk for CVD in younger individuals to a greater extent.

Individuals younger than 45 years with gout were more than twice as likely to develop CVD compared with similarly aged individuals without gout. For comparison, individuals aged 45-54 years with gout were 84% more likely to develop CVD, and individuals aged 55-64 years were 57% more likely to develop CVD than matched controls.

Conduction system disease had the highest incident risk (HR, 1.88), followed by heart failure and valve disease (HR, 1.85 for both).

Individuals with gout had higher rates of comorbidities than the controls, including hypertension, obesity, and dyslipidemia. Overall, CVD risk was slightly attenuated after adjustment for traditional CVD risk factors such as smoking, blood pressure, and body mass index but still significant: Patients with gout had a 31% higher risk for CVD than comparators.

This shows “that known CVD risk factors only explain part of the CVD risks seen in patients with gout,” Dr. Conrad said. Other factors such as inflammation and other disease activity factors could be at play, she explained, which would need to be explored in future research.

The study “shows the whole landscape” of CVD and gout, Michael H. Pillinger, MD, rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Grossman School of Medicine in New York City, said in an interview. He was not involved with the research.

“Every possible cardiovascular disease that they could think of was something that gout patients had more of than the non-gout patients,” he added. “I think this is going to be a paper that gets cited a lot, at minimum when describing the background of risk when we look at gout patients.”

The study had some limitations, including that researchers were unable to account for how medications such as nonsteroidal anti-inflammatory drugs, corticosteroids, colchicine, or allopurinol may have affected the association between gout and CVD.

“This is because analyses of nonrandomized treatment can be confounded by indication, wherein it is difficult to differentiate the effects of the treatment from underlying disease severity,” the authors wrote.

There was also a large amount of missing data on blood pressure, body mass index, smoking status, and other health information relevant to cardiovascular risk, so sensitivity analyses adjusting for these factors “should be interpreted with caution,” they added.

Dr. Pillinger also noted that the rates of comorbidities in the gout study population were lower than what have been found in US study populations. For example, about 40% of patients with gout in the analysis had hypertension, while other studies have suggested higher rates of 60%-70%, he said. However, it’s not clear if these differences could have affected outcomes. He added that these limitations do not “in any way weaken [the authors’] conclusion.”

The findings call for better strategies to reduce CVD risk in patients with gout, Dr. Conrad noted.

“Further improvements could come from better recognition and intervention on CVD risk factors (eg, through lifestyle changes or drug therapies where they are indicated), as well as proactive screening for heart disease in patients with gout, which could allow early diagnosis and interventions to delay more severe outcomes,” she added.

This study was funded by Research Foundation Flanders. Dr. Conrad was funded by a personal fellowship from the Research Foundation Flanders and a European Society of Cardiology research grant. She received royalties from Oxford University Innovation. Four of Dr. Conrad’s eight coauthors also reported financial relationships with pharmaceutical companies. Dr. Pillinger served as a consultant to Amgen, Federation Bio, Fortress Biotech, and Scilex, and he holds an investigator-initiated grant from Hikma.

A version of this article appeared on Medscape.com.

People with gout are 58% more likely to develop cardiovascular disease (CVD), according to a new analysis. This increased risk was observed across 12 different cardiovascular conditions, including heart failure, arrhythmias, and valve diseases.

“These findings suggest that the organ damage associated with gout is likely to be much broader than originally thought,” Nathalie Conrad, PhD, senior author of the research and cardiovascular epidemiologist at KU Leuven, Leuven, Belgium, said in an email. This could be useful for future research on underlying biological mechanisms driving CVD risk in gout, she added.

While previous research has tied gout to increased cardiovascular risk, these studies “largely focused on coronary heart disease, stroke, and thromboembolic outcomes,” she explained, and have been smaller in size.

This new study included more than 862,000 individuals, which permitted researchers to investigate rarer CVD outcomes such as myocarditis and pericarditis.

For the study, researchers used electronic health records from the UK Clinical Practice Research Datalink, a primary care database that contains anonymized health data for about 22 million individuals. Using these data, they identified more than 152,600 individuals with gout. Patients included in the analysis were diagnosed between 2000 and 2017, younger than 80 years at diagnosis, and free of CVD for at least 12 months after their gout diagnosis.

Patients with gout were compared with nearly 710,000 controls, matched on demographic factors such as age, sex, and geographic region.

Researchers then investigated the incidence of 12 CVDs, including atherosclerotic diseases, degenerative and thromboembolic diseases, and arrythmias, between the two groups from January 1, 2000, to June 30, 2019.

The findings were published in the March 2024 issue of The Lancet Rheumatology. Overall, patients with gout were 58% more likely to develop any CVD than their matched comparators without gout. There was a higher disease incidence among patients with gout for each of the 12 conditions. This association was more pronounced in women (hazard ratio [HR], 1.88) than in men (HR, 1.49), and gout amplified the risk for CVD in younger individuals to a greater extent.

Individuals younger than 45 years with gout were more than twice as likely to develop CVD compared with similarly aged individuals without gout. For comparison, individuals aged 45-54 years with gout were 84% more likely to develop CVD, and individuals aged 55-64 years were 57% more likely to develop CVD than matched controls.

Conduction system disease had the highest incident risk (HR, 1.88), followed by heart failure and valve disease (HR, 1.85 for both).

Individuals with gout had higher rates of comorbidities than the controls, including hypertension, obesity, and dyslipidemia. Overall, CVD risk was slightly attenuated after adjustment for traditional CVD risk factors such as smoking, blood pressure, and body mass index but still significant: Patients with gout had a 31% higher risk for CVD than comparators.

This shows “that known CVD risk factors only explain part of the CVD risks seen in patients with gout,” Dr. Conrad said. Other factors such as inflammation and other disease activity factors could be at play, she explained, which would need to be explored in future research.

The study “shows the whole landscape” of CVD and gout, Michael H. Pillinger, MD, rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Grossman School of Medicine in New York City, said in an interview. He was not involved with the research.

“Every possible cardiovascular disease that they could think of was something that gout patients had more of than the non-gout patients,” he added. “I think this is going to be a paper that gets cited a lot, at minimum when describing the background of risk when we look at gout patients.”

The study had some limitations, including that researchers were unable to account for how medications such as nonsteroidal anti-inflammatory drugs, corticosteroids, colchicine, or allopurinol may have affected the association between gout and CVD.

“This is because analyses of nonrandomized treatment can be confounded by indication, wherein it is difficult to differentiate the effects of the treatment from underlying disease severity,” the authors wrote.

There was also a large amount of missing data on blood pressure, body mass index, smoking status, and other health information relevant to cardiovascular risk, so sensitivity analyses adjusting for these factors “should be interpreted with caution,” they added.

Dr. Pillinger also noted that the rates of comorbidities in the gout study population were lower than what have been found in US study populations. For example, about 40% of patients with gout in the analysis had hypertension, while other studies have suggested higher rates of 60%-70%, he said. However, it’s not clear if these differences could have affected outcomes. He added that these limitations do not “in any way weaken [the authors’] conclusion.”

The findings call for better strategies to reduce CVD risk in patients with gout, Dr. Conrad noted.

“Further improvements could come from better recognition and intervention on CVD risk factors (eg, through lifestyle changes or drug therapies where they are indicated), as well as proactive screening for heart disease in patients with gout, which could allow early diagnosis and interventions to delay more severe outcomes,” she added.

This study was funded by Research Foundation Flanders. Dr. Conrad was funded by a personal fellowship from the Research Foundation Flanders and a European Society of Cardiology research grant. She received royalties from Oxford University Innovation. Four of Dr. Conrad’s eight coauthors also reported financial relationships with pharmaceutical companies. Dr. Pillinger served as a consultant to Amgen, Federation Bio, Fortress Biotech, and Scilex, and he holds an investigator-initiated grant from Hikma.

A version of this article appeared on Medscape.com.

For many, stretching is the fitness equivalent of awkward small talk. It’s the opening act, the thing you tolerate because you know it will be over soon. 

Others have challenged the practice, suggesting that stretching isn’t necessary at all. Some research has found that a preworkout stretch may even be disadvantageous, weakening muscles and hindering performance.

To put it plainly, no one seems terribly enthusiastic about touching their toes. 

That’s why a 2020 study on exercise and mortality was such a head-scratcher. The study found that stretching was uniquely associated with a lower risk for all-cause mortality among American adults. That’s after controlling for participation in other types of exercise. 

The finding seemed like a fluke, until a 2023 study found essentially the same thing. 

Among Korean adults, those who did flexibility exercise at least five times a week had a 20% lower risk of dying during the follow-up period than those who didn’t stretch at all. That was slightly better than the risk reduction associated with high volumes of aerobic exercise and resistance training. 

How can that be ? It turns out, stretching is linked to several health benefits that you might not expect.
 

The Surprising Benefits of Stretching

When we talk about stretching, we usually mean static stretching — getting into and holding a position that challenges a muscle, with the goal of improving range of motion around a joint. 

It doesn’t need to be a big challenge. “Research shows you can get increases in flexibility by stretching to the initial point of discomfort,” said David Behm, PhD, an exercise scientist at Memorial University of Newfoundland in Canada who’s published dozens of studies on stretching over the past quarter-century. 

That brings us to the first benefit.
 

Stretching Benefit #1: More Strength

At first glance, flexibility training and strength training have little in common. You lengthen muscles in the former and contract them in the latter. 

But in both cases, Dr. Behm said, you’re applying tension to muscles and connective tissues. Tension activates proteins called integrins, which send and receive signals across cellular membranes. Those signals are the start of a cascade that leads to protein synthesis. That’s how muscles get bigger and stronger when you lift weights. 

That mechanism could explain the small gains in muscle strength and size associated with static stretching, Dr. Behm said. 

But can you really stretch your way to muscle growth? Theoretically, yes. But strength training is far more time-efficient, Dr. Behm says. Studies showing increases in muscle mass have typically stretched a single muscle (usually the calves, using a specialized device) for > 30 min/session, 6 d/wk for 6 weeks. And that’s for just one leg.

Still, stretching may be more accessible for some patients — research suggested that older and more sedentary people are most likely to benefit from stretching-induced gains in strength.

 

Stretching Benefit #2: Reduced Arterial Stiffness

“Most people don’t think about the cardiovascular benefits of stretching,” Dr. Behm said. There are some big ones. 

If your body doesn’t move well, it’s not unreasonable to assume your blood doesn’t flow well. That is indeed the case: Poor flexibility is associated with arterial stiffness. 

Stretching is associated not only with improved arterial function but also with reductions in resting heart rate and blood pressure and increased vasodilation.

Mobility improvements may have an indirect benefit on cardiovascular health as well. 

“Studies show runners are more economical when they’re more flexible,” Dr. Behm said. If your movement is more efficient, you’ll probably do more of it. Doing more, in turn, would lead to improved fitness. 
 

Stretching Benefit #3: Improved Performance

Research is equivocal on whether stretching improves athletic performance, said Joe Yoon, a sports massage therapist in Orlando, Florida, and author of Better Stretching. 

“But I’ve always taken the approach that if you can improve your range of motion and get into positions” required for your sport, you’ll probably perform better, with less risk for injury, Mr. Yoon said. 

It’s worth noting that some research over the past 30 years has linked pre-exercise static stretching with a loss of strength, power, and/or speed. 

But consider this: In a 2016 review, Dr. Behm and his coauthors showed that performance reductions were most likely to occur in two situations: 

When participants did extremely long stretches (duration, ≥ 60 sec per muscle).

When researchers tested the participants’ strength, power, or speed immediately after they stretched.

Avoiding those problems is easy, Dr. Behm said: Stretch each muscle for < 60 sec, and combine static stretches with more active warm-up exercises. 

“Stretching can impair your performance but only if you do it wrong,” he said.
 

Stretching Benefit #4: Fewer Injuries

When you stretch, the point where you feel tension is where the muscle is most vulnerable. “That’s where injuries usually happen,” Dr. Behm said. 

More flexibility in those areas allows your muscles to safely generate force at longer lengths. For an athlete, that means fewer injuries when they’re doing explosive movements or changing direction. 

For nonathletes, flexibility reduces injuries by improving balance. Better balance reduces the risk of falling and helps mitigate the damage if you do take a tumble.
 

Help Your Patients Get the Benefits of Stretching

Stretching, like training for endurance or strength, can be as complex as you want to make it. But Mr. Yoon advocates a simpler approach. 

“You see this flashy stuff online,” he said. “But if you see those trainers in real life or you book a session with them, they go right back to the basics.” 

Ideally, Mr. Yoon said, a flexibility routine will work the entire body. But if that’s too big a stretch for your patient, he recommends starting with one or two stretches for the most problematic area. 

For example, for a stiff back, try doing the puppy pose at least once a day, although twice is better. Hold the position for 30 seconds to 2 minutes, said Mr. Yoon. Even if you combine it with a dynamic movement like the cat-cow, the two exercises would take just a few minutes a day. 

“There’s this misconception that you have to do a lot of it to be successful,” Mr. Yoon said. 

Consistency is far more important than volume. Mr. Yoon recommends “a little bit every day — the minimum viable dose.” 

As a bonus, stretching an area like your upper back will probably improve your shoulder mobility, Mr. Yoon said. Same with your lower body: Stretches for your hips, over time, should also benefit your knees and lower back. 

And thanks to a phenomenon called nonlocal flexibility transfer, lower-body stretches should improve upper-body flexibility, at least temporarily. Shoulder stretches can also have an immediate effect on hip mobility. 

“It’s all connected,” Mr. Yoon said, which brings us back to where we started. 

If stretching can indeed reduce mortality risk, it’s probably because of interconnected pathways, rather than any single mechanism. 

Most obviously, stretching improves flexibility, which makes movement easier, improves balance, and reduces the risk for falls and other types of injuries. It can also lead to small improvements in strength. Less obviously, stretching improves several aspects of cardiovascular function, including circulation. 

“There seems to be a global effect in everything we do,” Dr. Behm said. “Whether you’re stretching or weight training, the message is sent throughout your body."

A version of this article appeared on Medscape.com.

For many, stretching is the fitness equivalent of awkward small talk. It’s the opening act, the thing you tolerate because you know it will be over soon. 

Others have challenged the practice, suggesting that stretching isn’t necessary at all. Some research has found that a preworkout stretch may even be disadvantageous, weakening muscles and hindering performance.

To put it plainly, no one seems terribly enthusiastic about touching their toes. 

That’s why a 2020 study on exercise and mortality was such a head-scratcher. The study found that stretching was uniquely associated with a lower risk for all-cause mortality among American adults. That’s after controlling for participation in other types of exercise. 

The finding seemed like a fluke, until a 2023 study found essentially the same thing. 

Among Korean adults, those who did flexibility exercise at least five times a week had a 20% lower risk of dying during the follow-up period than those who didn’t stretch at all. That was slightly better than the risk reduction associated with high volumes of aerobic exercise and resistance training. 

How can that be ? It turns out, stretching is linked to several health benefits that you might not expect.
 

The Surprising Benefits of Stretching

When we talk about stretching, we usually mean static stretching — getting into and holding a position that challenges a muscle, with the goal of improving range of motion around a joint. 

It doesn’t need to be a big challenge. “Research shows you can get increases in flexibility by stretching to the initial point of discomfort,” said David Behm, PhD, an exercise scientist at Memorial University of Newfoundland in Canada who’s published dozens of studies on stretching over the past quarter-century. 

That brings us to the first benefit.
 

Stretching Benefit #1: More Strength

At first glance, flexibility training and strength training have little in common. You lengthen muscles in the former and contract them in the latter. 

But in both cases, Dr. Behm said, you’re applying tension to muscles and connective tissues. Tension activates proteins called integrins, which send and receive signals across cellular membranes. Those signals are the start of a cascade that leads to protein synthesis. That’s how muscles get bigger and stronger when you lift weights. 

That mechanism could explain the small gains in muscle strength and size associated with static stretching, Dr. Behm said. 

But can you really stretch your way to muscle growth? Theoretically, yes. But strength training is far more time-efficient, Dr. Behm says. Studies showing increases in muscle mass have typically stretched a single muscle (usually the calves, using a specialized device) for > 30 min/session, 6 d/wk for 6 weeks. And that’s for just one leg.

Still, stretching may be more accessible for some patients — research suggested that older and more sedentary people are most likely to benefit from stretching-induced gains in strength.

 

Stretching Benefit #2: Reduced Arterial Stiffness

“Most people don’t think about the cardiovascular benefits of stretching,” Dr. Behm said. There are some big ones. 

If your body doesn’t move well, it’s not unreasonable to assume your blood doesn’t flow well. That is indeed the case: Poor flexibility is associated with arterial stiffness. 

Stretching is associated not only with improved arterial function but also with reductions in resting heart rate and blood pressure and increased vasodilation.

Mobility improvements may have an indirect benefit on cardiovascular health as well. 

“Studies show runners are more economical when they’re more flexible,” Dr. Behm said. If your movement is more efficient, you’ll probably do more of it. Doing more, in turn, would lead to improved fitness. 
 

Stretching Benefit #3: Improved Performance

Research is equivocal on whether stretching improves athletic performance, said Joe Yoon, a sports massage therapist in Orlando, Florida, and author of Better Stretching. 

“But I’ve always taken the approach that if you can improve your range of motion and get into positions” required for your sport, you’ll probably perform better, with less risk for injury, Mr. Yoon said. 

It’s worth noting that some research over the past 30 years has linked pre-exercise static stretching with a loss of strength, power, and/or speed. 

But consider this: In a 2016 review, Dr. Behm and his coauthors showed that performance reductions were most likely to occur in two situations: 

When participants did extremely long stretches (duration, ≥ 60 sec per muscle).

When researchers tested the participants’ strength, power, or speed immediately after they stretched.

Avoiding those problems is easy, Dr. Behm said: Stretch each muscle for < 60 sec, and combine static stretches with more active warm-up exercises. 

“Stretching can impair your performance but only if you do it wrong,” he said.
 

Stretching Benefit #4: Fewer Injuries

When you stretch, the point where you feel tension is where the muscle is most vulnerable. “That’s where injuries usually happen,” Dr. Behm said. 

More flexibility in those areas allows your muscles to safely generate force at longer lengths. For an athlete, that means fewer injuries when they’re doing explosive movements or changing direction. 

For nonathletes, flexibility reduces injuries by improving balance. Better balance reduces the risk of falling and helps mitigate the damage if you do take a tumble.
 

Help Your Patients Get the Benefits of Stretching

Stretching, like training for endurance or strength, can be as complex as you want to make it. But Mr. Yoon advocates a simpler approach. 

“You see this flashy stuff online,” he said. “But if you see those trainers in real life or you book a session with them, they go right back to the basics.” 

Ideally, Mr. Yoon said, a flexibility routine will work the entire body. But if that’s too big a stretch for your patient, he recommends starting with one or two stretches for the most problematic area. 

For example, for a stiff back, try doing the puppy pose at least once a day, although twice is better. Hold the position for 30 seconds to 2 minutes, said Mr. Yoon. Even if you combine it with a dynamic movement like the cat-cow, the two exercises would take just a few minutes a day. 

“There’s this misconception that you have to do a lot of it to be successful,” Mr. Yoon said. 

Consistency is far more important than volume. Mr. Yoon recommends “a little bit every day — the minimum viable dose.” 

As a bonus, stretching an area like your upper back will probably improve your shoulder mobility, Mr. Yoon said. Same with your lower body: Stretches for your hips, over time, should also benefit your knees and lower back. 

And thanks to a phenomenon called nonlocal flexibility transfer, lower-body stretches should improve upper-body flexibility, at least temporarily. Shoulder stretches can also have an immediate effect on hip mobility. 

“It’s all connected,” Mr. Yoon said, which brings us back to where we started. 

If stretching can indeed reduce mortality risk, it’s probably because of interconnected pathways, rather than any single mechanism. 

Most obviously, stretching improves flexibility, which makes movement easier, improves balance, and reduces the risk for falls and other types of injuries. It can also lead to small improvements in strength. Less obviously, stretching improves several aspects of cardiovascular function, including circulation. 

“There seems to be a global effect in everything we do,” Dr. Behm said. “Whether you’re stretching or weight training, the message is sent throughout your body."

A version of this article appeared on Medscape.com.

For many, stretching is the fitness equivalent of awkward small talk. It’s the opening act, the thing you tolerate because you know it will be over soon. 

Others have challenged the practice, suggesting that stretching isn’t necessary at all. Some research has found that a preworkout stretch may even be disadvantageous, weakening muscles and hindering performance.

To put it plainly, no one seems terribly enthusiastic about touching their toes. 

That’s why a 2020 study on exercise and mortality was such a head-scratcher. The study found that stretching was uniquely associated with a lower risk for all-cause mortality among American adults. That’s after controlling for participation in other types of exercise. 

The finding seemed like a fluke, until a 2023 study found essentially the same thing. 

Among Korean adults, those who did flexibility exercise at least five times a week had a 20% lower risk of dying during the follow-up period than those who didn’t stretch at all. That was slightly better than the risk reduction associated with high volumes of aerobic exercise and resistance training. 

How can that be ? It turns out, stretching is linked to several health benefits that you might not expect.
 

The Surprising Benefits of Stretching

When we talk about stretching, we usually mean static stretching — getting into and holding a position that challenges a muscle, with the goal of improving range of motion around a joint. 

It doesn’t need to be a big challenge. “Research shows you can get increases in flexibility by stretching to the initial point of discomfort,” said David Behm, PhD, an exercise scientist at Memorial University of Newfoundland in Canada who’s published dozens of studies on stretching over the past quarter-century. 

That brings us to the first benefit.
 

Stretching Benefit #1: More Strength

At first glance, flexibility training and strength training have little in common. You lengthen muscles in the former and contract them in the latter. 

But in both cases, Dr. Behm said, you’re applying tension to muscles and connective tissues. Tension activates proteins called integrins, which send and receive signals across cellular membranes. Those signals are the start of a cascade that leads to protein synthesis. That’s how muscles get bigger and stronger when you lift weights. 

That mechanism could explain the small gains in muscle strength and size associated with static stretching, Dr. Behm said. 

But can you really stretch your way to muscle growth? Theoretically, yes. But strength training is far more time-efficient, Dr. Behm says. Studies showing increases in muscle mass have typically stretched a single muscle (usually the calves, using a specialized device) for > 30 min/session, 6 d/wk for 6 weeks. And that’s for just one leg.

Still, stretching may be more accessible for some patients — research suggested that older and more sedentary people are most likely to benefit from stretching-induced gains in strength.

 

Stretching Benefit #2: Reduced Arterial Stiffness

“Most people don’t think about the cardiovascular benefits of stretching,” Dr. Behm said. There are some big ones. 

If your body doesn’t move well, it’s not unreasonable to assume your blood doesn’t flow well. That is indeed the case: Poor flexibility is associated with arterial stiffness. 

Stretching is associated not only with improved arterial function but also with reductions in resting heart rate and blood pressure and increased vasodilation.

Mobility improvements may have an indirect benefit on cardiovascular health as well. 

“Studies show runners are more economical when they’re more flexible,” Dr. Behm said. If your movement is more efficient, you’ll probably do more of it. Doing more, in turn, would lead to improved fitness. 
 

Stretching Benefit #3: Improved Performance

Research is equivocal on whether stretching improves athletic performance, said Joe Yoon, a sports massage therapist in Orlando, Florida, and author of Better Stretching. 

“But I’ve always taken the approach that if you can improve your range of motion and get into positions” required for your sport, you’ll probably perform better, with less risk for injury, Mr. Yoon said. 

It’s worth noting that some research over the past 30 years has linked pre-exercise static stretching with a loss of strength, power, and/or speed. 

But consider this: In a 2016 review, Dr. Behm and his coauthors showed that performance reductions were most likely to occur in two situations: 

When participants did extremely long stretches (duration, ≥ 60 sec per muscle).

When researchers tested the participants’ strength, power, or speed immediately after they stretched.

Avoiding those problems is easy, Dr. Behm said: Stretch each muscle for < 60 sec, and combine static stretches with more active warm-up exercises. 

“Stretching can impair your performance but only if you do it wrong,” he said.
 

Stretching Benefit #4: Fewer Injuries

When you stretch, the point where you feel tension is where the muscle is most vulnerable. “That’s where injuries usually happen,” Dr. Behm said. 

More flexibility in those areas allows your muscles to safely generate force at longer lengths. For an athlete, that means fewer injuries when they’re doing explosive movements or changing direction. 

For nonathletes, flexibility reduces injuries by improving balance. Better balance reduces the risk of falling and helps mitigate the damage if you do take a tumble.
 

Help Your Patients Get the Benefits of Stretching

Stretching, like training for endurance or strength, can be as complex as you want to make it. But Mr. Yoon advocates a simpler approach. 

“You see this flashy stuff online,” he said. “But if you see those trainers in real life or you book a session with them, they go right back to the basics.” 

Ideally, Mr. Yoon said, a flexibility routine will work the entire body. But if that’s too big a stretch for your patient, he recommends starting with one or two stretches for the most problematic area. 

For example, for a stiff back, try doing the puppy pose at least once a day, although twice is better. Hold the position for 30 seconds to 2 minutes, said Mr. Yoon. Even if you combine it with a dynamic movement like the cat-cow, the two exercises would take just a few minutes a day. 

“There’s this misconception that you have to do a lot of it to be successful,” Mr. Yoon said. 

Consistency is far more important than volume. Mr. Yoon recommends “a little bit every day — the minimum viable dose.” 

As a bonus, stretching an area like your upper back will probably improve your shoulder mobility, Mr. Yoon said. Same with your lower body: Stretches for your hips, over time, should also benefit your knees and lower back. 

And thanks to a phenomenon called nonlocal flexibility transfer, lower-body stretches should improve upper-body flexibility, at least temporarily. Shoulder stretches can also have an immediate effect on hip mobility. 

“It’s all connected,” Mr. Yoon said, which brings us back to where we started. 

If stretching can indeed reduce mortality risk, it’s probably because of interconnected pathways, rather than any single mechanism. 

Most obviously, stretching improves flexibility, which makes movement easier, improves balance, and reduces the risk for falls and other types of injuries. It can also lead to small improvements in strength. Less obviously, stretching improves several aspects of cardiovascular function, including circulation. 

“There seems to be a global effect in everything we do,” Dr. Behm said. “Whether you’re stretching or weight training, the message is sent throughout your body."

A version of this article appeared on Medscape.com.