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Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

A higher percentage of family physicians quit during the early months of the pandemic than the average yearly percentage that did in the prior decade, according to data from Canada.

The researchers conducted two analyses of billing claims data for family physicians practicing in Ontario. They examined data for a period from 2010 to 2019 – before the onset of the pandemic – and from 2019 through 2020. The findings were published in Annals of Family Medicine.

Overall, the proportion of family physicians who stopped working rose from an average of 1.6% each year for the period between 2010 and 2019 to 3% in the period from 2019 to 2020. The pandemic data set included 12,247 physicians in Ontario. Of these, 385 (3.1%) reported no billings in the first 6 months of the pandemic.

Compared with family physicians billing for work during the pandemic, those reporting no billings were significantly more likely to be 75 years or older (13.0% vs. 3.4%), to have patient panels of less than 500 patients (40.0% vs. 25.8%), and to be eligible for fee-for-service reimbursement (37.7% vs. 24.9%; P less than .001 for all). The family physicians who reported no billing early in the pandemic also had fewer billing days in the previous year (mean of 73 days vs. 101 days, P less than .001).

In a regression analysis, the absolute increase in the percentage of family physicians who stopped working was 0.3% per year from 2010 to 2019, but rose to 1.2% between 2019 and 2020.

Challenges to family physicians in Ontario in the early months of the COVID-19 pandemic included reduced revenue, inability to keep offices fully staffed, and problems obtaining enough personal protective equipment. Such challenges may have prompted some family physicians to stop working prematurely, but more research is needed in other settings, wrote study author Tara Kiran, MD, of the University of Toronto, and colleagues.

“There were a lot of stories and suggestions that more family physicians were choosing to retire due to COVID,” Michael Green, MD, a coauthor of the paper, said in an interview. “Given the preexisting shortages we thought it would be important to see if this was true, and how big of an issue it was,” he said.

Although the absolute number of primary care physicians who stopped working is small, the implications are large given the ongoing shortage of family physicians in Canada, the researchers wrote.

The characteristics of physicians stopping work, such as older age and smaller practice size, were consistent with that of physicians preparing for retirement, the researchers noted. In addition, 56% of the family physicians who stopped working during the pandemic practiced in a patient enrollment model, in which patients are enrolled and between 15% and 70% of payment is based on age and sex. In this study, approximately 80% of physicians worked in this model. The remaining 20% operated in independent, fee-for-service practices.

“Although we cannot directly attribute causation, we hypothesize that some family physicians accelerated their retirement plans because of the pandemic,” the researchers noted. They proposed that possible reasons include health concerns, increased costs of infection prevention and control, reduced revenue from office visits, and burnout. The current study did not examine these issues.

Additional studies are needed to understand the impact on population health, the researchers concluded, but they estimated that the number of family physicians who stopped work during the pandemic would have provided care for approximately 170,000 patients.

The study findings reflect a genuine turnover by family physicians, vs. a departure from family practice to a fellowship and practice in another specialty, Dr. Green said. “We looked at physician billings to determine who stopped practicing, so we report only on those who stopped billing the Ontario Health Insurance Program altogether,” he explained.

The ongoing pandemic accelerated the issue of an upcoming wave of physician retirements and added to an already large number of people without a family physician, Dr. Green noted.

“We know there will be significant shortages of family physicians if we don’t modernize our ways of delivering primary care,” said Dr. Green. More research is needed on how to support family doctors with teams and administrative supports to allow them to provide high quality care to more patients, he said. Better models to estimate health workforce needs in primary care are needed as well, he added.

In the United States, a physician shortage has been growing since before the pandemic, according to a report published in 2021 by the Association of American Medical Colleges. In this report, “The Complexities of Physician Supply and Demand: Projections from 2019 to 2034,” the authors specifically projected a primary care physician shortage of 17,800 to 48,000 by 2034. This projection is in part based on an increase in the percentage of the U.S. population aged 65 years and older, which will increase the demand for care, according to the authors. The report also confirmed that many U.S. physicians are approaching retirement age and that more than two of five active physicians will be 65 years or older within the next 10 years.

However, the authors of this U.S. report acknowledged that the impact of the pandemic on existing primary care shortages remains unclear.

“There are still many unknowns about the direct short-term and long-term impacts of COVID-19 on the physician workforce, and it may be several years before those impacts are clearly understood,” they said in the executive summary of their report.

Alison N. Huffstetler, MD, a coauthor of a recent report that tried to identify the active primary care workforce in Virginia, said, “We know from other research that there are not enough primary care doctors, right now, to do the work that needs to be done – some citations have noted it would take a primary care doc over 20 hours a day just to provide preventive care.

“As our population continues to age, live longer, and need more complex care management, we must ensure we have an accountable, accessible, and knowledgeable primary care network to care for our communities,” she said.
 

Current state of primary care in Virginia

The study by Dr. Huffstetler, of Virginia Commonwealth University, Richmond, and colleagues was published in Annals of Family Medicine. It used a novel strategy involving the analysis of state all-payer claims data to determine how many physicians were practicing primary care in Virginia.

The researchers used the National Plan and Provider Enumeration System (NPPES) and the Virginia All-Payer Claims Database (VA-APCD) and identified all Virginia physicians and their specialties through the NPPES between 2015 and 2019. Active physicians were defined as those with at least one claim in the VA-APCD during the study period. They identified 20,976 active physicians in Virginia, 28.1% of whom were classified as primary care. Of these, 52% were family medicine physicians, 18.5% were internal medicine physicians, 16.8% were pediatricians, 11.8% were ob.gyns., and 0.5% were other specialists.

Clinician specialties were identified via specialty codes from the NPPES. Physicians were identified as primary care providers in two ways. The first way was by identifying those who had a National Uniform Claim Committee (NUCC) taxonomy of family medicine. The NUCC identifies a provider’s specialty using several levels of classification based on board certification and subspecialty certification data. The second identifier was having been a physician who had billed for at least 10 wellness visit codes from Jan. 1, 2019, through Dec. 31, 2019.

Over the 5-year study period (2015-2019), the counts and percentages of primary care physicians in the workforce remained stable, and the overall number of physicians in the state increased by 3.5%, the researchers noted. A total of 60.45% of all physicians and 60.87% of primary care physicians remained active, and 11.66% of all physicians had a claim in only 1 of the 5 years.
 

How distribution and access impact patients

In an interview, Dr. Huffstetler said the study she and colleagues authored “offers a transparent and reproducible process for identifying primary care physicians in a state, where they practice, and what changes in staffing occur over time.”

“In Virginia, this is particularly important, as we recently expanded Medicaid, making primary care more affordable for over 500,000 people,” she said. “We also saw the importance of distribution and accessibility to primary care over the past 3 years of COVID. In order to adequately prepare for community needs in the coming years, we must know who is providing primary care, and where they are.”

However, the model used in this study has its limitations, Dr. Huffstetler said, including the lack of a definitive definition of primary care using claims data.

“We used a data-informed wellness visit threshold, but it is likely that primary care is delivered in some locations without claims that are reflected by a wellness visit, and we hope to look at scope in the future to help refine these results,” she said.
 

Canadian study shows pandemic’s impact on patient care

“The pandemic’s impact on primary care remains palpable, and Dr. Kiran’s team has done an excellent analysis on the practice trends during the past several years,” Dr. Huffstetler said.

“The Canadian analysis uses claims in a similar manner to our study; however, it appears that they already knew who the FPs were in Ontario,” Dr. Huffstetler noted. “Their claims threshold of 50 for active practice was higher than ours, at only 1. Should those FPs have moved to a different specialty, the physicians would still have claims for the patients seen in other subspecialties. As such, I don’t suspect that their analysis miscalculated those that transitioned, rather than stopped practice,” she explained.

The Ontario study was supported by the Initial Credential Evaluation Service, which is funded by the Ontario Ministry of Health and the Ministry of Long-Term Care, as well as by the Canadian Institutes of Health Research. Additional support came from the INSPIRE Primary Health Care Research Program, which is also funded by the Ontario Ministry of Health and Long-Term Care. The researchers had no financial conflicts to disclose.

The Virginia study was supported by the Department of Medical Assistance Services and the National Center for Advancing Translational Sciences. The researchers had no financial conflicts to disclose.

The supply and demand report was conducted for the AAMC by IHS Markit, a global information company.

A higher percentage of family physicians quit during the early months of the pandemic than the average yearly percentage that did in the prior decade, according to data from Canada.

The researchers conducted two analyses of billing claims data for family physicians practicing in Ontario. They examined data for a period from 2010 to 2019 – before the onset of the pandemic – and from 2019 through 2020. The findings were published in Annals of Family Medicine.

Overall, the proportion of family physicians who stopped working rose from an average of 1.6% each year for the period between 2010 and 2019 to 3% in the period from 2019 to 2020. The pandemic data set included 12,247 physicians in Ontario. Of these, 385 (3.1%) reported no billings in the first 6 months of the pandemic.

Compared with family physicians billing for work during the pandemic, those reporting no billings were significantly more likely to be 75 years or older (13.0% vs. 3.4%), to have patient panels of less than 500 patients (40.0% vs. 25.8%), and to be eligible for fee-for-service reimbursement (37.7% vs. 24.9%; P less than .001 for all). The family physicians who reported no billing early in the pandemic also had fewer billing days in the previous year (mean of 73 days vs. 101 days, P less than .001).

In a regression analysis, the absolute increase in the percentage of family physicians who stopped working was 0.3% per year from 2010 to 2019, but rose to 1.2% between 2019 and 2020.

Challenges to family physicians in Ontario in the early months of the COVID-19 pandemic included reduced revenue, inability to keep offices fully staffed, and problems obtaining enough personal protective equipment. Such challenges may have prompted some family physicians to stop working prematurely, but more research is needed in other settings, wrote study author Tara Kiran, MD, of the University of Toronto, and colleagues.

“There were a lot of stories and suggestions that more family physicians were choosing to retire due to COVID,” Michael Green, MD, a coauthor of the paper, said in an interview. “Given the preexisting shortages we thought it would be important to see if this was true, and how big of an issue it was,” he said.

Although the absolute number of primary care physicians who stopped working is small, the implications are large given the ongoing shortage of family physicians in Canada, the researchers wrote.

The characteristics of physicians stopping work, such as older age and smaller practice size, were consistent with that of physicians preparing for retirement, the researchers noted. In addition, 56% of the family physicians who stopped working during the pandemic practiced in a patient enrollment model, in which patients are enrolled and between 15% and 70% of payment is based on age and sex. In this study, approximately 80% of physicians worked in this model. The remaining 20% operated in independent, fee-for-service practices.

“Although we cannot directly attribute causation, we hypothesize that some family physicians accelerated their retirement plans because of the pandemic,” the researchers noted. They proposed that possible reasons include health concerns, increased costs of infection prevention and control, reduced revenue from office visits, and burnout. The current study did not examine these issues.

Additional studies are needed to understand the impact on population health, the researchers concluded, but they estimated that the number of family physicians who stopped work during the pandemic would have provided care for approximately 170,000 patients.

The study findings reflect a genuine turnover by family physicians, vs. a departure from family practice to a fellowship and practice in another specialty, Dr. Green said. “We looked at physician billings to determine who stopped practicing, so we report only on those who stopped billing the Ontario Health Insurance Program altogether,” he explained.

The ongoing pandemic accelerated the issue of an upcoming wave of physician retirements and added to an already large number of people without a family physician, Dr. Green noted.

“We know there will be significant shortages of family physicians if we don’t modernize our ways of delivering primary care,” said Dr. Green. More research is needed on how to support family doctors with teams and administrative supports to allow them to provide high quality care to more patients, he said. Better models to estimate health workforce needs in primary care are needed as well, he added.

In the United States, a physician shortage has been growing since before the pandemic, according to a report published in 2021 by the Association of American Medical Colleges. In this report, “The Complexities of Physician Supply and Demand: Projections from 2019 to 2034,” the authors specifically projected a primary care physician shortage of 17,800 to 48,000 by 2034. This projection is in part based on an increase in the percentage of the U.S. population aged 65 years and older, which will increase the demand for care, according to the authors. The report also confirmed that many U.S. physicians are approaching retirement age and that more than two of five active physicians will be 65 years or older within the next 10 years.

However, the authors of this U.S. report acknowledged that the impact of the pandemic on existing primary care shortages remains unclear.

“There are still many unknowns about the direct short-term and long-term impacts of COVID-19 on the physician workforce, and it may be several years before those impacts are clearly understood,” they said in the executive summary of their report.

Alison N. Huffstetler, MD, a coauthor of a recent report that tried to identify the active primary care workforce in Virginia, said, “We know from other research that there are not enough primary care doctors, right now, to do the work that needs to be done – some citations have noted it would take a primary care doc over 20 hours a day just to provide preventive care.

“As our population continues to age, live longer, and need more complex care management, we must ensure we have an accountable, accessible, and knowledgeable primary care network to care for our communities,” she said.
 

Current state of primary care in Virginia

The study by Dr. Huffstetler, of Virginia Commonwealth University, Richmond, and colleagues was published in Annals of Family Medicine. It used a novel strategy involving the analysis of state all-payer claims data to determine how many physicians were practicing primary care in Virginia.

The researchers used the National Plan and Provider Enumeration System (NPPES) and the Virginia All-Payer Claims Database (VA-APCD) and identified all Virginia physicians and their specialties through the NPPES between 2015 and 2019. Active physicians were defined as those with at least one claim in the VA-APCD during the study period. They identified 20,976 active physicians in Virginia, 28.1% of whom were classified as primary care. Of these, 52% were family medicine physicians, 18.5% were internal medicine physicians, 16.8% were pediatricians, 11.8% were ob.gyns., and 0.5% were other specialists.

Clinician specialties were identified via specialty codes from the NPPES. Physicians were identified as primary care providers in two ways. The first way was by identifying those who had a National Uniform Claim Committee (NUCC) taxonomy of family medicine. The NUCC identifies a provider’s specialty using several levels of classification based on board certification and subspecialty certification data. The second identifier was having been a physician who had billed for at least 10 wellness visit codes from Jan. 1, 2019, through Dec. 31, 2019.

Over the 5-year study period (2015-2019), the counts and percentages of primary care physicians in the workforce remained stable, and the overall number of physicians in the state increased by 3.5%, the researchers noted. A total of 60.45% of all physicians and 60.87% of primary care physicians remained active, and 11.66% of all physicians had a claim in only 1 of the 5 years.
 

How distribution and access impact patients

In an interview, Dr. Huffstetler said the study she and colleagues authored “offers a transparent and reproducible process for identifying primary care physicians in a state, where they practice, and what changes in staffing occur over time.”

“In Virginia, this is particularly important, as we recently expanded Medicaid, making primary care more affordable for over 500,000 people,” she said. “We also saw the importance of distribution and accessibility to primary care over the past 3 years of COVID. In order to adequately prepare for community needs in the coming years, we must know who is providing primary care, and where they are.”

However, the model used in this study has its limitations, Dr. Huffstetler said, including the lack of a definitive definition of primary care using claims data.

“We used a data-informed wellness visit threshold, but it is likely that primary care is delivered in some locations without claims that are reflected by a wellness visit, and we hope to look at scope in the future to help refine these results,” she said.
 

Canadian study shows pandemic’s impact on patient care

“The pandemic’s impact on primary care remains palpable, and Dr. Kiran’s team has done an excellent analysis on the practice trends during the past several years,” Dr. Huffstetler said.

“The Canadian analysis uses claims in a similar manner to our study; however, it appears that they already knew who the FPs were in Ontario,” Dr. Huffstetler noted. “Their claims threshold of 50 for active practice was higher than ours, at only 1. Should those FPs have moved to a different specialty, the physicians would still have claims for the patients seen in other subspecialties. As such, I don’t suspect that their analysis miscalculated those that transitioned, rather than stopped practice,” she explained.

The Ontario study was supported by the Initial Credential Evaluation Service, which is funded by the Ontario Ministry of Health and the Ministry of Long-Term Care, as well as by the Canadian Institutes of Health Research. Additional support came from the INSPIRE Primary Health Care Research Program, which is also funded by the Ontario Ministry of Health and Long-Term Care. The researchers had no financial conflicts to disclose.

The Virginia study was supported by the Department of Medical Assistance Services and the National Center for Advancing Translational Sciences. The researchers had no financial conflicts to disclose.

The supply and demand report was conducted for the AAMC by IHS Markit, a global information company.

A higher percentage of family physicians quit during the early months of the pandemic than the average yearly percentage that did in the prior decade, according to data from Canada.

The researchers conducted two analyses of billing claims data for family physicians practicing in Ontario. They examined data for a period from 2010 to 2019 – before the onset of the pandemic – and from 2019 through 2020. The findings were published in Annals of Family Medicine.

Overall, the proportion of family physicians who stopped working rose from an average of 1.6% each year for the period between 2010 and 2019 to 3% in the period from 2019 to 2020. The pandemic data set included 12,247 physicians in Ontario. Of these, 385 (3.1%) reported no billings in the first 6 months of the pandemic.

Compared with family physicians billing for work during the pandemic, those reporting no billings were significantly more likely to be 75 years or older (13.0% vs. 3.4%), to have patient panels of less than 500 patients (40.0% vs. 25.8%), and to be eligible for fee-for-service reimbursement (37.7% vs. 24.9%; P less than .001 for all). The family physicians who reported no billing early in the pandemic also had fewer billing days in the previous year (mean of 73 days vs. 101 days, P less than .001).

In a regression analysis, the absolute increase in the percentage of family physicians who stopped working was 0.3% per year from 2010 to 2019, but rose to 1.2% between 2019 and 2020.

Challenges to family physicians in Ontario in the early months of the COVID-19 pandemic included reduced revenue, inability to keep offices fully staffed, and problems obtaining enough personal protective equipment. Such challenges may have prompted some family physicians to stop working prematurely, but more research is needed in other settings, wrote study author Tara Kiran, MD, of the University of Toronto, and colleagues.

“There were a lot of stories and suggestions that more family physicians were choosing to retire due to COVID,” Michael Green, MD, a coauthor of the paper, said in an interview. “Given the preexisting shortages we thought it would be important to see if this was true, and how big of an issue it was,” he said.

Although the absolute number of primary care physicians who stopped working is small, the implications are large given the ongoing shortage of family physicians in Canada, the researchers wrote.

The characteristics of physicians stopping work, such as older age and smaller practice size, were consistent with that of physicians preparing for retirement, the researchers noted. In addition, 56% of the family physicians who stopped working during the pandemic practiced in a patient enrollment model, in which patients are enrolled and between 15% and 70% of payment is based on age and sex. In this study, approximately 80% of physicians worked in this model. The remaining 20% operated in independent, fee-for-service practices.

“Although we cannot directly attribute causation, we hypothesize that some family physicians accelerated their retirement plans because of the pandemic,” the researchers noted. They proposed that possible reasons include health concerns, increased costs of infection prevention and control, reduced revenue from office visits, and burnout. The current study did not examine these issues.

Additional studies are needed to understand the impact on population health, the researchers concluded, but they estimated that the number of family physicians who stopped work during the pandemic would have provided care for approximately 170,000 patients.

The study findings reflect a genuine turnover by family physicians, vs. a departure from family practice to a fellowship and practice in another specialty, Dr. Green said. “We looked at physician billings to determine who stopped practicing, so we report only on those who stopped billing the Ontario Health Insurance Program altogether,” he explained.

The ongoing pandemic accelerated the issue of an upcoming wave of physician retirements and added to an already large number of people without a family physician, Dr. Green noted.

“We know there will be significant shortages of family physicians if we don’t modernize our ways of delivering primary care,” said Dr. Green. More research is needed on how to support family doctors with teams and administrative supports to allow them to provide high quality care to more patients, he said. Better models to estimate health workforce needs in primary care are needed as well, he added.

In the United States, a physician shortage has been growing since before the pandemic, according to a report published in 2021 by the Association of American Medical Colleges. In this report, “The Complexities of Physician Supply and Demand: Projections from 2019 to 2034,” the authors specifically projected a primary care physician shortage of 17,800 to 48,000 by 2034. This projection is in part based on an increase in the percentage of the U.S. population aged 65 years and older, which will increase the demand for care, according to the authors. The report also confirmed that many U.S. physicians are approaching retirement age and that more than two of five active physicians will be 65 years or older within the next 10 years.

However, the authors of this U.S. report acknowledged that the impact of the pandemic on existing primary care shortages remains unclear.

“There are still many unknowns about the direct short-term and long-term impacts of COVID-19 on the physician workforce, and it may be several years before those impacts are clearly understood,” they said in the executive summary of their report.

Alison N. Huffstetler, MD, a coauthor of a recent report that tried to identify the active primary care workforce in Virginia, said, “We know from other research that there are not enough primary care doctors, right now, to do the work that needs to be done – some citations have noted it would take a primary care doc over 20 hours a day just to provide preventive care.

“As our population continues to age, live longer, and need more complex care management, we must ensure we have an accountable, accessible, and knowledgeable primary care network to care for our communities,” she said.
 

Current state of primary care in Virginia

The study by Dr. Huffstetler, of Virginia Commonwealth University, Richmond, and colleagues was published in Annals of Family Medicine. It used a novel strategy involving the analysis of state all-payer claims data to determine how many physicians were practicing primary care in Virginia.

The researchers used the National Plan and Provider Enumeration System (NPPES) and the Virginia All-Payer Claims Database (VA-APCD) and identified all Virginia physicians and their specialties through the NPPES between 2015 and 2019. Active physicians were defined as those with at least one claim in the VA-APCD during the study period. They identified 20,976 active physicians in Virginia, 28.1% of whom were classified as primary care. Of these, 52% were family medicine physicians, 18.5% were internal medicine physicians, 16.8% were pediatricians, 11.8% were ob.gyns., and 0.5% were other specialists.

Clinician specialties were identified via specialty codes from the NPPES. Physicians were identified as primary care providers in two ways. The first way was by identifying those who had a National Uniform Claim Committee (NUCC) taxonomy of family medicine. The NUCC identifies a provider’s specialty using several levels of classification based on board certification and subspecialty certification data. The second identifier was having been a physician who had billed for at least 10 wellness visit codes from Jan. 1, 2019, through Dec. 31, 2019.

Over the 5-year study period (2015-2019), the counts and percentages of primary care physicians in the workforce remained stable, and the overall number of physicians in the state increased by 3.5%, the researchers noted. A total of 60.45% of all physicians and 60.87% of primary care physicians remained active, and 11.66% of all physicians had a claim in only 1 of the 5 years.
 

How distribution and access impact patients

In an interview, Dr. Huffstetler said the study she and colleagues authored “offers a transparent and reproducible process for identifying primary care physicians in a state, where they practice, and what changes in staffing occur over time.”

“In Virginia, this is particularly important, as we recently expanded Medicaid, making primary care more affordable for over 500,000 people,” she said. “We also saw the importance of distribution and accessibility to primary care over the past 3 years of COVID. In order to adequately prepare for community needs in the coming years, we must know who is providing primary care, and where they are.”

However, the model used in this study has its limitations, Dr. Huffstetler said, including the lack of a definitive definition of primary care using claims data.

“We used a data-informed wellness visit threshold, but it is likely that primary care is delivered in some locations without claims that are reflected by a wellness visit, and we hope to look at scope in the future to help refine these results,” she said.
 

Canadian study shows pandemic’s impact on patient care

“The pandemic’s impact on primary care remains palpable, and Dr. Kiran’s team has done an excellent analysis on the practice trends during the past several years,” Dr. Huffstetler said.

“The Canadian analysis uses claims in a similar manner to our study; however, it appears that they already knew who the FPs were in Ontario,” Dr. Huffstetler noted. “Their claims threshold of 50 for active practice was higher than ours, at only 1. Should those FPs have moved to a different specialty, the physicians would still have claims for the patients seen in other subspecialties. As such, I don’t suspect that their analysis miscalculated those that transitioned, rather than stopped practice,” she explained.

The Ontario study was supported by the Initial Credential Evaluation Service, which is funded by the Ontario Ministry of Health and the Ministry of Long-Term Care, as well as by the Canadian Institutes of Health Research. Additional support came from the INSPIRE Primary Health Care Research Program, which is also funded by the Ontario Ministry of Health and Long-Term Care. The researchers had no financial conflicts to disclose.

The Virginia study was supported by the Department of Medical Assistance Services and the National Center for Advancing Translational Sciences. The researchers had no financial conflicts to disclose.

The supply and demand report was conducted for the AAMC by IHS Markit, a global information company.

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

Bariatric surgery may raise the risk of developing epilepsy, new research suggests. Analyzing health records, investigators compared almost 17,000 patients who had undergone bariatric surgery with more than 620,000 individuals with obesity who had not undergone the surgery.

During a minimum 3-year follow-up period, the surgery group had a 45% higher risk of developing epilepsy than the nonsurgery group. Moreover, patients who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.

“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” senior investigator Jorge Burneo, MD, professor of neurology, biostatistics, and epidemiology and endowed chair in epilepsy at Western University, London, told this news organization.

“While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss,” Dr. Burneo said.

The findings were published online in Neurology.
 

Unrecognized risk factor?

Bariatric surgery has become more common as global rates of obesity have increased. The surgery has been shown to reduce the risk for serious obesity-related conditions, the researchers note.

However, “in addition to the positive outcomes of bariatric surgery, several long-term neurological complications have also been identified,” they write.

One previous study reported increased epilepsy risk following gastric bypass. Those findings “suggest that bariatric surgery may be an unrecognized epilepsy risk factor; however, this possible association has not been thoroughly explored,” write the investigators.

Dr. Burneo said he conducted the study because he has seen patients with epilepsy in his clinic who were “without risk factors, with normal MRIs, who shared the history of having bariatric surgery before the development of epilepsy.”

The researchers’ primary objective was to “assess whether epilepsy risk is elevated following bariatric surgery for weight loss relative to a nonsurgical cohort of patients who are obese,” he noted.

The study used linked administrative health databases in Ontario, Canada. Patients were accrued from July 1, 2010, to Dec. 31, 2016, and were followed until Dec. 31, 2019. The analysis included 639,472 participants, 2.7% of whom had undergone bariatric surgery.

The “exposed” cohort consisted of all Ontario residents aged 18 years or older who had undergone bariatric surgery during the 6-year period (n = 16,958; 65.1% women; mean age, 47.4 years), while the “unexposed” cohort consisted of patients hospitalized with a diagnosis of obesity who had not undergone bariatric surgery (n = 622,514; 62.8% women; mean age, 47.6 years).

Patients with a history of seizures, epilepsy, epilepsy risk factors, prior brain surgery, psychiatric disorders, or drug or alcohol abuse/dependence were excluded from the analysis.

The researchers collected data on patients’ sociodemographic characteristics at the index date, as well as Charlson Comorbidity Index scores during the 2 years prior to index, and data regarding several specific comorbidities, such as diabetes mellitus, hypertension, sleep apnea, depression/anxiety, and cardiovascular factors.

The exposed and unexposed cohorts were followed for a median period of 5.8 and 5.9 person-years, respectively.
 

‘Unclear’ mechanisms

Before weighting, 0.4% of participants in the exposed cohort (n = 73) developed epilepsy, versus 0.2% of participants in the unexposed cohort (n = 1,260) by the end of the follow-up period.

In the weighted cohorts, there were 50.1 epilepsy diagnoses per 100,000 person-years, versus 34.1 per 100,000 person-years (rate difference, 16 per 100,000 person-years).

The multivariable analysis of the weighted cohort showed the hazard ratio for epilepsy cases that were associated with bariatric surgery was 1.45 (95% confidence interval, 1.35-1.56), after adjusting for sleep apnea and including stroke as a time-varying covariate.

Having a stroke during the follow-up period increased epilepsy 14-fold in the exposed cohort (HR, 14.03; 95% CI, 4.25-46.25).

The investigators note that they were unable to measure obesity status or body mass index throughout the study and that some obesity-related comorbidities “may affect epilepsy risk.”

In addition, Dr. Burneo reported that the study did not investigate potential causes and mechanisms of the association between bariatric surgery and epilepsy risk.

Hypotheses “include potential nutritional deficiencies, receipt of general anesthesia, or other unclear causes,” he said.

“Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure,” Dr. Burneo added.
 

Risk-benefit discussion

In a comment, Jacqueline French, MD, professor of neurology at NYU Grossman School of Medicine, and director of NYU’s Epilepsy Study Consortium, said she was “not 100% surprised by the findings” because she has seen in her clinical practice “a number of patients who developed epilepsy after bariatric surgery or had a history of bariatric surgery at the time they developed epilepsy.”

On the other hand, she has also seen patients who did not have a history of bariatric surgery and who developed epilepsy.

“I’m unable to tell if there is an association, although I’ve had it at the back of my head as a thought and wondered about it,” said Dr. French, who is also the chief medical and innovation officer at the Epilepsy Foundation. She was not involved with the study.

She noted that possible mechanisms underlying the association are that gastric bypass surgery leads to a “significant alteration” in nutrient absorption. Moreover, “we now know that the microbiome is associated with epilepsy” and that changes occur in the gut microbiome after bariatric surgery, Dr. French said.

There are two take-home messages for practicing clinicians, she added.

“Although the risk [of developing epilepsy] is very low, it should be presented as part of the risks and benefits to patients considering bariatric surgery,” she said.

“It’s equally important to follow up on the potential differences in these patients who go on to develop epilepsy following bariatric surgery,” said Dr. French. “Is there a certain metabolic profile or some nutrient previously absorbed that now is not absorbed that might predispose people to risk?”

This would be “enormously important to know because it might not just pertain to these people but to a whole other cohort of people who develop epilepsy,” Dr. French concluded.

The study was funded by the Ontario Ministry of Health and Ministry of Long-Term Care and by the Jack Cowin Endowed Chair in Epilepsy Research at Western University. Dr. Burneo holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. The other investigators and Dr. French have reported no relevant financial relationships.

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

Bariatric surgery may raise the risk of developing epilepsy, new research suggests. Analyzing health records, investigators compared almost 17,000 patients who had undergone bariatric surgery with more than 620,000 individuals with obesity who had not undergone the surgery.

During a minimum 3-year follow-up period, the surgery group had a 45% higher risk of developing epilepsy than the nonsurgery group. Moreover, patients who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.

“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” senior investigator Jorge Burneo, MD, professor of neurology, biostatistics, and epidemiology and endowed chair in epilepsy at Western University, London, told this news organization.

“While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss,” Dr. Burneo said.

The findings were published online in Neurology.
 

Unrecognized risk factor?

Bariatric surgery has become more common as global rates of obesity have increased. The surgery has been shown to reduce the risk for serious obesity-related conditions, the researchers note.

However, “in addition to the positive outcomes of bariatric surgery, several long-term neurological complications have also been identified,” they write.

One previous study reported increased epilepsy risk following gastric bypass. Those findings “suggest that bariatric surgery may be an unrecognized epilepsy risk factor; however, this possible association has not been thoroughly explored,” write the investigators.

Dr. Burneo said he conducted the study because he has seen patients with epilepsy in his clinic who were “without risk factors, with normal MRIs, who shared the history of having bariatric surgery before the development of epilepsy.”

The researchers’ primary objective was to “assess whether epilepsy risk is elevated following bariatric surgery for weight loss relative to a nonsurgical cohort of patients who are obese,” he noted.

The study used linked administrative health databases in Ontario, Canada. Patients were accrued from July 1, 2010, to Dec. 31, 2016, and were followed until Dec. 31, 2019. The analysis included 639,472 participants, 2.7% of whom had undergone bariatric surgery.

The “exposed” cohort consisted of all Ontario residents aged 18 years or older who had undergone bariatric surgery during the 6-year period (n = 16,958; 65.1% women; mean age, 47.4 years), while the “unexposed” cohort consisted of patients hospitalized with a diagnosis of obesity who had not undergone bariatric surgery (n = 622,514; 62.8% women; mean age, 47.6 years).

Patients with a history of seizures, epilepsy, epilepsy risk factors, prior brain surgery, psychiatric disorders, or drug or alcohol abuse/dependence were excluded from the analysis.

The researchers collected data on patients’ sociodemographic characteristics at the index date, as well as Charlson Comorbidity Index scores during the 2 years prior to index, and data regarding several specific comorbidities, such as diabetes mellitus, hypertension, sleep apnea, depression/anxiety, and cardiovascular factors.

The exposed and unexposed cohorts were followed for a median period of 5.8 and 5.9 person-years, respectively.
 

‘Unclear’ mechanisms

Before weighting, 0.4% of participants in the exposed cohort (n = 73) developed epilepsy, versus 0.2% of participants in the unexposed cohort (n = 1,260) by the end of the follow-up period.

In the weighted cohorts, there were 50.1 epilepsy diagnoses per 100,000 person-years, versus 34.1 per 100,000 person-years (rate difference, 16 per 100,000 person-years).

The multivariable analysis of the weighted cohort showed the hazard ratio for epilepsy cases that were associated with bariatric surgery was 1.45 (95% confidence interval, 1.35-1.56), after adjusting for sleep apnea and including stroke as a time-varying covariate.

Having a stroke during the follow-up period increased epilepsy 14-fold in the exposed cohort (HR, 14.03; 95% CI, 4.25-46.25).

The investigators note that they were unable to measure obesity status or body mass index throughout the study and that some obesity-related comorbidities “may affect epilepsy risk.”

In addition, Dr. Burneo reported that the study did not investigate potential causes and mechanisms of the association between bariatric surgery and epilepsy risk.

Hypotheses “include potential nutritional deficiencies, receipt of general anesthesia, or other unclear causes,” he said.

“Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure,” Dr. Burneo added.
 

Risk-benefit discussion

In a comment, Jacqueline French, MD, professor of neurology at NYU Grossman School of Medicine, and director of NYU’s Epilepsy Study Consortium, said she was “not 100% surprised by the findings” because she has seen in her clinical practice “a number of patients who developed epilepsy after bariatric surgery or had a history of bariatric surgery at the time they developed epilepsy.”

On the other hand, she has also seen patients who did not have a history of bariatric surgery and who developed epilepsy.

“I’m unable to tell if there is an association, although I’ve had it at the back of my head as a thought and wondered about it,” said Dr. French, who is also the chief medical and innovation officer at the Epilepsy Foundation. She was not involved with the study.

She noted that possible mechanisms underlying the association are that gastric bypass surgery leads to a “significant alteration” in nutrient absorption. Moreover, “we now know that the microbiome is associated with epilepsy” and that changes occur in the gut microbiome after bariatric surgery, Dr. French said.

There are two take-home messages for practicing clinicians, she added.

“Although the risk [of developing epilepsy] is very low, it should be presented as part of the risks and benefits to patients considering bariatric surgery,” she said.

“It’s equally important to follow up on the potential differences in these patients who go on to develop epilepsy following bariatric surgery,” said Dr. French. “Is there a certain metabolic profile or some nutrient previously absorbed that now is not absorbed that might predispose people to risk?”

This would be “enormously important to know because it might not just pertain to these people but to a whole other cohort of people who develop epilepsy,” Dr. French concluded.

The study was funded by the Ontario Ministry of Health and Ministry of Long-Term Care and by the Jack Cowin Endowed Chair in Epilepsy Research at Western University. Dr. Burneo holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. The other investigators and Dr. French have reported no relevant financial relationships.

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

Bariatric surgery may raise the risk of developing epilepsy, new research suggests. Analyzing health records, investigators compared almost 17,000 patients who had undergone bariatric surgery with more than 620,000 individuals with obesity who had not undergone the surgery.

During a minimum 3-year follow-up period, the surgery group had a 45% higher risk of developing epilepsy than the nonsurgery group. Moreover, patients who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.

“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” senior investigator Jorge Burneo, MD, professor of neurology, biostatistics, and epidemiology and endowed chair in epilepsy at Western University, London, told this news organization.

“While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss,” Dr. Burneo said.

The findings were published online in Neurology.
 

Unrecognized risk factor?

Bariatric surgery has become more common as global rates of obesity have increased. The surgery has been shown to reduce the risk for serious obesity-related conditions, the researchers note.

However, “in addition to the positive outcomes of bariatric surgery, several long-term neurological complications have also been identified,” they write.

One previous study reported increased epilepsy risk following gastric bypass. Those findings “suggest that bariatric surgery may be an unrecognized epilepsy risk factor; however, this possible association has not been thoroughly explored,” write the investigators.

Dr. Burneo said he conducted the study because he has seen patients with epilepsy in his clinic who were “without risk factors, with normal MRIs, who shared the history of having bariatric surgery before the development of epilepsy.”

The researchers’ primary objective was to “assess whether epilepsy risk is elevated following bariatric surgery for weight loss relative to a nonsurgical cohort of patients who are obese,” he noted.

The study used linked administrative health databases in Ontario, Canada. Patients were accrued from July 1, 2010, to Dec. 31, 2016, and were followed until Dec. 31, 2019. The analysis included 639,472 participants, 2.7% of whom had undergone bariatric surgery.

The “exposed” cohort consisted of all Ontario residents aged 18 years or older who had undergone bariatric surgery during the 6-year period (n = 16,958; 65.1% women; mean age, 47.4 years), while the “unexposed” cohort consisted of patients hospitalized with a diagnosis of obesity who had not undergone bariatric surgery (n = 622,514; 62.8% women; mean age, 47.6 years).

Patients with a history of seizures, epilepsy, epilepsy risk factors, prior brain surgery, psychiatric disorders, or drug or alcohol abuse/dependence were excluded from the analysis.

The researchers collected data on patients’ sociodemographic characteristics at the index date, as well as Charlson Comorbidity Index scores during the 2 years prior to index, and data regarding several specific comorbidities, such as diabetes mellitus, hypertension, sleep apnea, depression/anxiety, and cardiovascular factors.

The exposed and unexposed cohorts were followed for a median period of 5.8 and 5.9 person-years, respectively.
 

‘Unclear’ mechanisms

Before weighting, 0.4% of participants in the exposed cohort (n = 73) developed epilepsy, versus 0.2% of participants in the unexposed cohort (n = 1,260) by the end of the follow-up period.

In the weighted cohorts, there were 50.1 epilepsy diagnoses per 100,000 person-years, versus 34.1 per 100,000 person-years (rate difference, 16 per 100,000 person-years).

The multivariable analysis of the weighted cohort showed the hazard ratio for epilepsy cases that were associated with bariatric surgery was 1.45 (95% confidence interval, 1.35-1.56), after adjusting for sleep apnea and including stroke as a time-varying covariate.

Having a stroke during the follow-up period increased epilepsy 14-fold in the exposed cohort (HR, 14.03; 95% CI, 4.25-46.25).

The investigators note that they were unable to measure obesity status or body mass index throughout the study and that some obesity-related comorbidities “may affect epilepsy risk.”

In addition, Dr. Burneo reported that the study did not investigate potential causes and mechanisms of the association between bariatric surgery and epilepsy risk.

Hypotheses “include potential nutritional deficiencies, receipt of general anesthesia, or other unclear causes,” he said.

“Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure,” Dr. Burneo added.
 

Risk-benefit discussion

In a comment, Jacqueline French, MD, professor of neurology at NYU Grossman School of Medicine, and director of NYU’s Epilepsy Study Consortium, said she was “not 100% surprised by the findings” because she has seen in her clinical practice “a number of patients who developed epilepsy after bariatric surgery or had a history of bariatric surgery at the time they developed epilepsy.”

On the other hand, she has also seen patients who did not have a history of bariatric surgery and who developed epilepsy.

“I’m unable to tell if there is an association, although I’ve had it at the back of my head as a thought and wondered about it,” said Dr. French, who is also the chief medical and innovation officer at the Epilepsy Foundation. She was not involved with the study.

She noted that possible mechanisms underlying the association are that gastric bypass surgery leads to a “significant alteration” in nutrient absorption. Moreover, “we now know that the microbiome is associated with epilepsy” and that changes occur in the gut microbiome after bariatric surgery, Dr. French said.

There are two take-home messages for practicing clinicians, she added.

“Although the risk [of developing epilepsy] is very low, it should be presented as part of the risks and benefits to patients considering bariatric surgery,” she said.

“It’s equally important to follow up on the potential differences in these patients who go on to develop epilepsy following bariatric surgery,” said Dr. French. “Is there a certain metabolic profile or some nutrient previously absorbed that now is not absorbed that might predispose people to risk?”

This would be “enormously important to know because it might not just pertain to these people but to a whole other cohort of people who develop epilepsy,” Dr. French concluded.

The study was funded by the Ontario Ministry of Health and Ministry of Long-Term Care and by the Jack Cowin Endowed Chair in Epilepsy Research at Western University. Dr. Burneo holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. The other investigators and Dr. French have reported no relevant financial relationships.

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

Researchers published the study covered in this summary on Preprints with The Lancet as a preprint that has not yet been peer reviewed.

Key takeaways

• Adults in China who consumed a “balanced,” moderate ratio (middle three quintiles) of animal-to-vegetable cooking oil had a lower rate of developing type 2 diabetes during a median follow-up of 8.6 years, compared with those who consumed the lowest ratio (first quintile), after multivariable adjustment using prospectively collected data.
• The results also indicate that increasing animal cooking oil (such as lard, tallow, or butter) and vegetable cooking oil (such as peanut or soybean oil) consumption were each positively associated with a higher rate of developing type 2 diabetes.
• Those who consumed the highest ratio (fifth quintile) of animal-to-vegetable cooking oil had a nonsignificant difference in their rate of developing type 2 diabetes, compared with those in the first quintile.

Why this matters

• The findings suggest that consuming a diet with a “balanced” moderate intake of animal and vegetable oil might lower the risk of type 2 diabetes, which would reduce disease burden and health care expenditures.
• The results imply that using a single source of cooking oil, either animal or vegetable, contributes to the incidence of type 2 diabetes.
• This is the first large epidemiological study showing a relationship between the ratio of animal- and vegetable-derived fats in people’s diets and their risk for incident type 2 diabetes.

Study design

• The researchers used data collected prospectively starting in 2010-2012 from 7,274 adult residents of Guizhou province, China, with follow-up assessment in 2020 after a median of 8.6 years.
• At baseline, participants underwent an oral glucose tolerance test and provided information on demographics, family medical history, and personal medical history, including whether they had been diagnosed with type 2 diabetes or were taking antihyperglycemic medications. The study did not include anyone with a history of diabetes.
• Data on intake of animal and vegetable cooking oil came from a dietary questionnaire.
• The authors calculated hazard ratios for development of type 2 diabetes after adjusting for multiple potential confounders.

Key results

• The study cohort averaged 44 years old, and 53% were women.
• During a median follow-up of 8.6 years, 747 people developed type 2 diabetes.
• Compared with those who had the lowest intake of animal cooking oil (first quintile), those with the highest intake (fifth quintile) had a significant 28% increased relative rate for developing type 2 diabetes after adjustment for several potential confounders.
• Compared with those with the lowest intake of vegetable cooking oil, those with the highest intake had a significant 56% increased rate of developing type 2 diabetes after adjustment.
• Compared with adults with the lowest animal-to-vegetable cooking oil ratio (first quintile), those in the second, third, and fourth quintiles for this ratio had significantly lower adjusted relative rates of developing type 2 diabetes, with adjusted hazard ratios of 0.79, 0.65, and 0.68, respectively. Those in the highest quintile (fifth quintile) did not have a significantly different risk, compared with the first quintile.
• The protective effect of a balanced ratio of animal-to-vegetable cooking oils was stronger in people who lived in rural districts and in those who had obesity.

Limitations

• The dietary information came from participants’ self-reports, which may have produced biased data.
• The study only included information about animal and vegetable cooking oil consumed at home.
• There may have been residual confounding from variables not included in the study.
• The time of diagnosis of type 2 diabetes may have been inaccurate because follow-up occurred only once. 
• The study may have underestimated the incidence of type 2 diabetes because of a lack of information about hemoglobin A1c levels at follow-up.

Disclosures

• The study did not receive commercial funding.
• The authors reported no financial disclosures.

This is a summary of a preprint article “The consumption ratio of animal cooking oil to vegetable cooking oil and reduced risk of type 2 diabetes mellitus: A prospective cohort study in Southwest China” written by researchers primarily from Zunyi Medical University, China, on Preprints with The Lancet. This study has not yet been peer reviewed. The full text of the study can be found on papers.ssrn.com.

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

Researchers published the study covered in this summary on Preprints with The Lancet as a preprint that has not yet been peer reviewed.

Key takeaways

• Adults in China who consumed a “balanced,” moderate ratio (middle three quintiles) of animal-to-vegetable cooking oil had a lower rate of developing type 2 diabetes during a median follow-up of 8.6 years, compared with those who consumed the lowest ratio (first quintile), after multivariable adjustment using prospectively collected data.
• The results also indicate that increasing animal cooking oil (such as lard, tallow, or butter) and vegetable cooking oil (such as peanut or soybean oil) consumption were each positively associated with a higher rate of developing type 2 diabetes.
• Those who consumed the highest ratio (fifth quintile) of animal-to-vegetable cooking oil had a nonsignificant difference in their rate of developing type 2 diabetes, compared with those in the first quintile.

Why this matters

• The findings suggest that consuming a diet with a “balanced” moderate intake of animal and vegetable oil might lower the risk of type 2 diabetes, which would reduce disease burden and health care expenditures.
• The results imply that using a single source of cooking oil, either animal or vegetable, contributes to the incidence of type 2 diabetes.
• This is the first large epidemiological study showing a relationship between the ratio of animal- and vegetable-derived fats in people’s diets and their risk for incident type 2 diabetes.

Study design

• The researchers used data collected prospectively starting in 2010-2012 from 7,274 adult residents of Guizhou province, China, with follow-up assessment in 2020 after a median of 8.6 years.
• At baseline, participants underwent an oral glucose tolerance test and provided information on demographics, family medical history, and personal medical history, including whether they had been diagnosed with type 2 diabetes or were taking antihyperglycemic medications. The study did not include anyone with a history of diabetes.
• Data on intake of animal and vegetable cooking oil came from a dietary questionnaire.
• The authors calculated hazard ratios for development of type 2 diabetes after adjusting for multiple potential confounders.

Key results

• The study cohort averaged 44 years old, and 53% were women.
• During a median follow-up of 8.6 years, 747 people developed type 2 diabetes.
• Compared with those who had the lowest intake of animal cooking oil (first quintile), those with the highest intake (fifth quintile) had a significant 28% increased relative rate for developing type 2 diabetes after adjustment for several potential confounders.
• Compared with those with the lowest intake of vegetable cooking oil, those with the highest intake had a significant 56% increased rate of developing type 2 diabetes after adjustment.
• Compared with adults with the lowest animal-to-vegetable cooking oil ratio (first quintile), those in the second, third, and fourth quintiles for this ratio had significantly lower adjusted relative rates of developing type 2 diabetes, with adjusted hazard ratios of 0.79, 0.65, and 0.68, respectively. Those in the highest quintile (fifth quintile) did not have a significantly different risk, compared with the first quintile.
• The protective effect of a balanced ratio of animal-to-vegetable cooking oils was stronger in people who lived in rural districts and in those who had obesity.

Limitations

• The dietary information came from participants’ self-reports, which may have produced biased data.
• The study only included information about animal and vegetable cooking oil consumed at home.
• There may have been residual confounding from variables not included in the study.
• The time of diagnosis of type 2 diabetes may have been inaccurate because follow-up occurred only once. 
• The study may have underestimated the incidence of type 2 diabetes because of a lack of information about hemoglobin A1c levels at follow-up.

Disclosures

• The study did not receive commercial funding.
• The authors reported no financial disclosures.

This is a summary of a preprint article “The consumption ratio of animal cooking oil to vegetable cooking oil and reduced risk of type 2 diabetes mellitus: A prospective cohort study in Southwest China” written by researchers primarily from Zunyi Medical University, China, on Preprints with The Lancet. This study has not yet been peer reviewed. The full text of the study can be found on papers.ssrn.com.

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

Researchers published the study covered in this summary on Preprints with The Lancet as a preprint that has not yet been peer reviewed.

Key takeaways

• Adults in China who consumed a “balanced,” moderate ratio (middle three quintiles) of animal-to-vegetable cooking oil had a lower rate of developing type 2 diabetes during a median follow-up of 8.6 years, compared with those who consumed the lowest ratio (first quintile), after multivariable adjustment using prospectively collected data.
• The results also indicate that increasing animal cooking oil (such as lard, tallow, or butter) and vegetable cooking oil (such as peanut or soybean oil) consumption were each positively associated with a higher rate of developing type 2 diabetes.
• Those who consumed the highest ratio (fifth quintile) of animal-to-vegetable cooking oil had a nonsignificant difference in their rate of developing type 2 diabetes, compared with those in the first quintile.

Why this matters

• The findings suggest that consuming a diet with a “balanced” moderate intake of animal and vegetable oil might lower the risk of type 2 diabetes, which would reduce disease burden and health care expenditures.
• The results imply that using a single source of cooking oil, either animal or vegetable, contributes to the incidence of type 2 diabetes.
• This is the first large epidemiological study showing a relationship between the ratio of animal- and vegetable-derived fats in people’s diets and their risk for incident type 2 diabetes.

Study design

• The researchers used data collected prospectively starting in 2010-2012 from 7,274 adult residents of Guizhou province, China, with follow-up assessment in 2020 after a median of 8.6 years.
• At baseline, participants underwent an oral glucose tolerance test and provided information on demographics, family medical history, and personal medical history, including whether they had been diagnosed with type 2 diabetes or were taking antihyperglycemic medications. The study did not include anyone with a history of diabetes.
• Data on intake of animal and vegetable cooking oil came from a dietary questionnaire.
• The authors calculated hazard ratios for development of type 2 diabetes after adjusting for multiple potential confounders.

Key results

• The study cohort averaged 44 years old, and 53% were women.
• During a median follow-up of 8.6 years, 747 people developed type 2 diabetes.
• Compared with those who had the lowest intake of animal cooking oil (first quintile), those with the highest intake (fifth quintile) had a significant 28% increased relative rate for developing type 2 diabetes after adjustment for several potential confounders.
• Compared with those with the lowest intake of vegetable cooking oil, those with the highest intake had a significant 56% increased rate of developing type 2 diabetes after adjustment.
• Compared with adults with the lowest animal-to-vegetable cooking oil ratio (first quintile), those in the second, third, and fourth quintiles for this ratio had significantly lower adjusted relative rates of developing type 2 diabetes, with adjusted hazard ratios of 0.79, 0.65, and 0.68, respectively. Those in the highest quintile (fifth quintile) did not have a significantly different risk, compared with the first quintile.
• The protective effect of a balanced ratio of animal-to-vegetable cooking oils was stronger in people who lived in rural districts and in those who had obesity.

Limitations

• The dietary information came from participants’ self-reports, which may have produced biased data.
• The study only included information about animal and vegetable cooking oil consumed at home.
• There may have been residual confounding from variables not included in the study.
• The time of diagnosis of type 2 diabetes may have been inaccurate because follow-up occurred only once. 
• The study may have underestimated the incidence of type 2 diabetes because of a lack of information about hemoglobin A1c levels at follow-up.

Disclosures

• The study did not receive commercial funding.
• The authors reported no financial disclosures.

This is a summary of a preprint article “The consumption ratio of animal cooking oil to vegetable cooking oil and reduced risk of type 2 diabetes mellitus: A prospective cohort study in Southwest China” written by researchers primarily from Zunyi Medical University, China, on Preprints with The Lancet. This study has not yet been peer reviewed. The full text of the study can be found on papers.ssrn.com.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

The Centers for Disease Control has changed its position on mandatory masking in health care settings, no longer recommending that it be universal.

It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.

“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.

The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.

Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.

About 73% of the country is having “high” rates of transmission, The Hill said.

“Community transmission” is different from the “community level” metric that’s used for non–health care settings. 

Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”

Just 7% of counties are considered high risk, while nearly 62 percent are low.

The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.

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

The Centers for Disease Control has changed its position on mandatory masking in health care settings, no longer recommending that it be universal.

It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.

“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.

The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.

Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.

About 73% of the country is having “high” rates of transmission, The Hill said.

“Community transmission” is different from the “community level” metric that’s used for non–health care settings. 

Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”

Just 7% of counties are considered high risk, while nearly 62 percent are low.

The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.

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

The Centers for Disease Control has changed its position on mandatory masking in health care settings, no longer recommending that it be universal.

It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.

“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.

The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.

Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.

About 73% of the country is having “high” rates of transmission, The Hill said.

“Community transmission” is different from the “community level” metric that’s used for non–health care settings. 

Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”

Just 7% of counties are considered high risk, while nearly 62 percent are low.

The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy who develop potentially serious neurotoxicity from the therapy show elevated plasma levels of neurofilament light chain (NfL) prior to the treatment, suggesting a possibly important predictor of risk for the side effect.

“This is the first study to show NfL levels are elevated even before CAR T treatment is given,” first author Omar H. Butt, MD, PhD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, said in an interview.

“While unlikely to be the sole driver of [the neurotoxicity], neural injury reflected by NfL may aid in identifying a high-risk subset of patients undergoing cellular therapy,” the authors concluded in the study, published in JAMA Oncology.

CAR T-cell therapy has gained favor for virtually revolutionizing the treatment of some leukemias and lymphomas, however, as many as 40%-60% of patients develop the neurotoxicity side effect, called immune effector cell–associated neurotoxicity syndrome (ICANS), which, though usually low grade, in more severe cases can cause substantial morbidity and even mortality.

Hence, “the early identification of patients at risk for ICANS is critical for preemptive management,” the authors noted.

NfL, an established marker of neuroaxonal injury in neurodegenerative diseases including multiple sclerosis and Alzheimer’s disease, has been shown in previous studies to be elevated following the development of ICANS and up to 5 days prior to its peak symptoms.

To further evaluate NfL elevations in relation to ICANS, Dr. Butt and colleagues identified 30 patients undergoing CD19 CART-cell therapy, including 77% for diffuse large B-cell lymphoma, at two U.S. centers: Washington University in St. Louis and Case Western Reserve University, Cleveland.

The patients had a median age of 64 and were 40% female.

Among them, four developed low-grade ICANS grade 1-2, and 7 developed ICANS grade 3 or higher.

Of those developing any-grade ICANS, baseline elevations of NfL prior to the CAR T-cell treatment, were significantly higher, compared with those who did not develop ICANs (mean 87.6 pg/mL vs. 29.4 pg/mL, P < .001), with no significant differences between the low-grade (1 and 2) and higher-grade (3 or higher) ICANS groups.

A receiver operating characteristic analysis showed baseline NfL levels significantly predicted the development of ICANS with high accuracy (area under the ROC curve, 0.96), as well as sensitivity (AUROC, 0.91) and specificity (AUROC, 0.95).

Notably, baseline NfL levels were associated with ICANS severity, but did not correlate with other factors including demographic, oncologic history, nononcologic neurologic history, or history of exposure to neurotoxic therapies.

However, Dr. Butt added, “it is important to note that our study was insufficiently powered to examine those relationships in earnest. Therefore, [a correlation between NfL and those factors] remains possible,” he said.

The elevated NfL levels observed prior to the development of ICANS remained high across the study’s seven time points, up to day 30 post infusion.
 

Interest in NfL levels on the rise

NfL assessment is currently only clinically validated in amyotrophic lateral sclerosis, where it is used to assess neuroaxonal health and integrity. However, testing is available as interest and evidence of NfL’s potential role in other settings grows.

Meanwhile, Dr. Butt and associates are themselves developing an assay to predict the development of ICANS, which will likely include NfL, if the role is validated in further studies.

“Future studies will explore validating NfL for ICANS and additional indications,” he said.

ICANS symptoms can range from headaches and confusion to seizures or strokes in more severe cases.

The current gold standard for treatment includes early intervention with high-dose steroids and careful monitoring, but there is reluctance to use such therapies because of concerns about their blunting the anticancer effects of the CAR T cells.

Importantly, if validated, elevations in NfL could signal the need for more precautionary measures with CAR T-cell therapy, Dr. Butt noted.

“Our data suggests patients with high NfL levels at baseline would benefit most from perhaps closer monitoring with frequent checks and possible early intervention at the first sign of symptoms, a period of time when it may be hard to distinguish ICANS from other causes of confusion, such as delirium,” he explained.
 

Limitations: Validation, preventive measures needed

Commenting on the study, Sattva S. Neelapu, MD, a professor and deputy chair of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, agreed that the findings have potentially important implications.

“I think this is a very intriguing and novel finding that needs to be investigated further prospectively in a larger cohort and across different CAR T products in patients with lymphoma, leukemia, and myeloma,” Dr. Neelapu said in an interview.

The NfL elevations observed even before CAR T-cell therapy among those who went on to develop ICANS are notable, he added.

“This is the surprising finding in the study,” Dr. Neelapu said. “It raises the question whether neurologic injury is caused by prior therapies that these patients received or whether it is an age-related phenomenon, as we do see higher incidence and severity of ICANS in older patients or some other mechanisms.”

A key caveat, however, is that even if a risk is identified, options to prevent ICANS are currently limited, Dr. Neelapu noted.

“I think it is too early to implement this into clinical practice,” he said. In addition to needing further validation, “assessing NfL levels would be useful when there is an effective prophylactic or therapeutic strategy – both of which also need to be investigated.”

Dr. Butt and colleagues are developing a clinical assay for ICANS and reported a provisional patent pending on the use of plasma NfL as a predictive biomarker for ICANS. The study received support from the Washington University in St. Louis, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, the Fred Simmons and Olga Mohan Fund; the National Cancer Institute, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Neelapu reported conflicts of interest with numerous pharmaceutical companies.

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy who develop potentially serious neurotoxicity from the therapy show elevated plasma levels of neurofilament light chain (NfL) prior to the treatment, suggesting a possibly important predictor of risk for the side effect.

“This is the first study to show NfL levels are elevated even before CAR T treatment is given,” first author Omar H. Butt, MD, PhD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, said in an interview.

“While unlikely to be the sole driver of [the neurotoxicity], neural injury reflected by NfL may aid in identifying a high-risk subset of patients undergoing cellular therapy,” the authors concluded in the study, published in JAMA Oncology.

CAR T-cell therapy has gained favor for virtually revolutionizing the treatment of some leukemias and lymphomas, however, as many as 40%-60% of patients develop the neurotoxicity side effect, called immune effector cell–associated neurotoxicity syndrome (ICANS), which, though usually low grade, in more severe cases can cause substantial morbidity and even mortality.

Hence, “the early identification of patients at risk for ICANS is critical for preemptive management,” the authors noted.

NfL, an established marker of neuroaxonal injury in neurodegenerative diseases including multiple sclerosis and Alzheimer’s disease, has been shown in previous studies to be elevated following the development of ICANS and up to 5 days prior to its peak symptoms.

To further evaluate NfL elevations in relation to ICANS, Dr. Butt and colleagues identified 30 patients undergoing CD19 CART-cell therapy, including 77% for diffuse large B-cell lymphoma, at two U.S. centers: Washington University in St. Louis and Case Western Reserve University, Cleveland.

The patients had a median age of 64 and were 40% female.

Among them, four developed low-grade ICANS grade 1-2, and 7 developed ICANS grade 3 or higher.

Of those developing any-grade ICANS, baseline elevations of NfL prior to the CAR T-cell treatment, were significantly higher, compared with those who did not develop ICANs (mean 87.6 pg/mL vs. 29.4 pg/mL, P < .001), with no significant differences between the low-grade (1 and 2) and higher-grade (3 or higher) ICANS groups.

A receiver operating characteristic analysis showed baseline NfL levels significantly predicted the development of ICANS with high accuracy (area under the ROC curve, 0.96), as well as sensitivity (AUROC, 0.91) and specificity (AUROC, 0.95).

Notably, baseline NfL levels were associated with ICANS severity, but did not correlate with other factors including demographic, oncologic history, nononcologic neurologic history, or history of exposure to neurotoxic therapies.

However, Dr. Butt added, “it is important to note that our study was insufficiently powered to examine those relationships in earnest. Therefore, [a correlation between NfL and those factors] remains possible,” he said.

The elevated NfL levels observed prior to the development of ICANS remained high across the study’s seven time points, up to day 30 post infusion.
 

Interest in NfL levels on the rise

NfL assessment is currently only clinically validated in amyotrophic lateral sclerosis, where it is used to assess neuroaxonal health and integrity. However, testing is available as interest and evidence of NfL’s potential role in other settings grows.

Meanwhile, Dr. Butt and associates are themselves developing an assay to predict the development of ICANS, which will likely include NfL, if the role is validated in further studies.

“Future studies will explore validating NfL for ICANS and additional indications,” he said.

ICANS symptoms can range from headaches and confusion to seizures or strokes in more severe cases.

The current gold standard for treatment includes early intervention with high-dose steroids and careful monitoring, but there is reluctance to use such therapies because of concerns about their blunting the anticancer effects of the CAR T cells.

Importantly, if validated, elevations in NfL could signal the need for more precautionary measures with CAR T-cell therapy, Dr. Butt noted.

“Our data suggests patients with high NfL levels at baseline would benefit most from perhaps closer monitoring with frequent checks and possible early intervention at the first sign of symptoms, a period of time when it may be hard to distinguish ICANS from other causes of confusion, such as delirium,” he explained.
 

Limitations: Validation, preventive measures needed

Commenting on the study, Sattva S. Neelapu, MD, a professor and deputy chair of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, agreed that the findings have potentially important implications.

“I think this is a very intriguing and novel finding that needs to be investigated further prospectively in a larger cohort and across different CAR T products in patients with lymphoma, leukemia, and myeloma,” Dr. Neelapu said in an interview.

The NfL elevations observed even before CAR T-cell therapy among those who went on to develop ICANS are notable, he added.

“This is the surprising finding in the study,” Dr. Neelapu said. “It raises the question whether neurologic injury is caused by prior therapies that these patients received or whether it is an age-related phenomenon, as we do see higher incidence and severity of ICANS in older patients or some other mechanisms.”

A key caveat, however, is that even if a risk is identified, options to prevent ICANS are currently limited, Dr. Neelapu noted.

“I think it is too early to implement this into clinical practice,” he said. In addition to needing further validation, “assessing NfL levels would be useful when there is an effective prophylactic or therapeutic strategy – both of which also need to be investigated.”

Dr. Butt and colleagues are developing a clinical assay for ICANS and reported a provisional patent pending on the use of plasma NfL as a predictive biomarker for ICANS. The study received support from the Washington University in St. Louis, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, the Fred Simmons and Olga Mohan Fund; the National Cancer Institute, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Neelapu reported conflicts of interest with numerous pharmaceutical companies.

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy who develop potentially serious neurotoxicity from the therapy show elevated plasma levels of neurofilament light chain (NfL) prior to the treatment, suggesting a possibly important predictor of risk for the side effect.

“This is the first study to show NfL levels are elevated even before CAR T treatment is given,” first author Omar H. Butt, MD, PhD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, said in an interview.

“While unlikely to be the sole driver of [the neurotoxicity], neural injury reflected by NfL may aid in identifying a high-risk subset of patients undergoing cellular therapy,” the authors concluded in the study, published in JAMA Oncology.

CAR T-cell therapy has gained favor for virtually revolutionizing the treatment of some leukemias and lymphomas, however, as many as 40%-60% of patients develop the neurotoxicity side effect, called immune effector cell–associated neurotoxicity syndrome (ICANS), which, though usually low grade, in more severe cases can cause substantial morbidity and even mortality.

Hence, “the early identification of patients at risk for ICANS is critical for preemptive management,” the authors noted.

NfL, an established marker of neuroaxonal injury in neurodegenerative diseases including multiple sclerosis and Alzheimer’s disease, has been shown in previous studies to be elevated following the development of ICANS and up to 5 days prior to its peak symptoms.

To further evaluate NfL elevations in relation to ICANS, Dr. Butt and colleagues identified 30 patients undergoing CD19 CART-cell therapy, including 77% for diffuse large B-cell lymphoma, at two U.S. centers: Washington University in St. Louis and Case Western Reserve University, Cleveland.

The patients had a median age of 64 and were 40% female.

Among them, four developed low-grade ICANS grade 1-2, and 7 developed ICANS grade 3 or higher.

Of those developing any-grade ICANS, baseline elevations of NfL prior to the CAR T-cell treatment, were significantly higher, compared with those who did not develop ICANs (mean 87.6 pg/mL vs. 29.4 pg/mL, P < .001), with no significant differences between the low-grade (1 and 2) and higher-grade (3 or higher) ICANS groups.

A receiver operating characteristic analysis showed baseline NfL levels significantly predicted the development of ICANS with high accuracy (area under the ROC curve, 0.96), as well as sensitivity (AUROC, 0.91) and specificity (AUROC, 0.95).

Notably, baseline NfL levels were associated with ICANS severity, but did not correlate with other factors including demographic, oncologic history, nononcologic neurologic history, or history of exposure to neurotoxic therapies.

However, Dr. Butt added, “it is important to note that our study was insufficiently powered to examine those relationships in earnest. Therefore, [a correlation between NfL and those factors] remains possible,” he said.

The elevated NfL levels observed prior to the development of ICANS remained high across the study’s seven time points, up to day 30 post infusion.
 

Interest in NfL levels on the rise

NfL assessment is currently only clinically validated in amyotrophic lateral sclerosis, where it is used to assess neuroaxonal health and integrity. However, testing is available as interest and evidence of NfL’s potential role in other settings grows.

Meanwhile, Dr. Butt and associates are themselves developing an assay to predict the development of ICANS, which will likely include NfL, if the role is validated in further studies.

“Future studies will explore validating NfL for ICANS and additional indications,” he said.

ICANS symptoms can range from headaches and confusion to seizures or strokes in more severe cases.

The current gold standard for treatment includes early intervention with high-dose steroids and careful monitoring, but there is reluctance to use such therapies because of concerns about their blunting the anticancer effects of the CAR T cells.

Importantly, if validated, elevations in NfL could signal the need for more precautionary measures with CAR T-cell therapy, Dr. Butt noted.

“Our data suggests patients with high NfL levels at baseline would benefit most from perhaps closer monitoring with frequent checks and possible early intervention at the first sign of symptoms, a period of time when it may be hard to distinguish ICANS from other causes of confusion, such as delirium,” he explained.
 

Limitations: Validation, preventive measures needed

Commenting on the study, Sattva S. Neelapu, MD, a professor and deputy chair of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, agreed that the findings have potentially important implications.

“I think this is a very intriguing and novel finding that needs to be investigated further prospectively in a larger cohort and across different CAR T products in patients with lymphoma, leukemia, and myeloma,” Dr. Neelapu said in an interview.

The NfL elevations observed even before CAR T-cell therapy among those who went on to develop ICANS are notable, he added.

“This is the surprising finding in the study,” Dr. Neelapu said. “It raises the question whether neurologic injury is caused by prior therapies that these patients received or whether it is an age-related phenomenon, as we do see higher incidence and severity of ICANS in older patients or some other mechanisms.”

A key caveat, however, is that even if a risk is identified, options to prevent ICANS are currently limited, Dr. Neelapu noted.

“I think it is too early to implement this into clinical practice,” he said. In addition to needing further validation, “assessing NfL levels would be useful when there is an effective prophylactic or therapeutic strategy – both of which also need to be investigated.”

Dr. Butt and colleagues are developing a clinical assay for ICANS and reported a provisional patent pending on the use of plasma NfL as a predictive biomarker for ICANS. The study received support from the Washington University in St. Louis, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, the Fred Simmons and Olga Mohan Fund; the National Cancer Institute, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Neelapu reported conflicts of interest with numerous pharmaceutical companies.