Neurology Reviews

A regimen of daily, low-dose aspirin failed to produce a significant reduction in the incidence of dementia or cognitive impairment in ASCEND, a randomized, multicenter trial with more than 15,000 people with diabetes followed for an average of more than 9 years, but the results hinted at enough of a benefit to warrant further study, some experts said.

jimdeli/Fotolia

A second metric used a broader outcome definition that tracked EHR entries for not only dementia but also diagnoses of cognitive impairment, delirium, confusion, prescription of dementia medications, and referral to a memory clinic or geriatric psychiatry. The third assessment was a cognitive-function test given to participants at the end of follow-up, but only 58% of enrolled participants completed this part of the study, and it’s also possible that some subjects missed this assessment because of dementia onset. These limitations hamper clear interpretation of this third metric, Dr. Armitage said.

The main findings for the other two, more reliable measures of incident dementia or cognitive deterioration showed a nonsignificant 9% relative risk reduction linked with aspirin use compared with placebo for the more inclusive endpoint, and a nonsignificant 11% relative risk reduction with aspirin using the narrow definition for dementia only, she reported. The third method, a directly administered assessment of dementia and cognition, also showed a small, nonsignificant effect from daily aspirin use relative to placebo.

Results can’t rule out modest aspirin effect

Dr. Armitage highlighted that the two more reliable measures both appeared to rule out risk for neurologic harm from aspirin because the upper limit of the 95% confidence interval for relative effect reached only 1.02 using the broad outcomes, and 1.06 for the narrower endpoint of dementia only. On the other hand, focus on the low end of the 95% confidence interval suggested potentially meaningful benefits, with a possible reduction by aspirin in events relative to placebo of as much as 19% by the broad outcome definition and by 25% with the narrow definition.

“Even if it was only a 15% relative risk reduction, that would be important,” given the high dementia incidence worldwide, Dr. Armitage said during a press briefing. “It’s entirely possible, with our results, that a modest benefit exists.”

This take on the findings won some support. Further studies with more people, longer follow-up, and perhaps enrolling a more selected, higher risk cohort may better address potential neurologic benefit from aspirin, suggested Amytis Towfighi, MD, a stroke neurologist and professor of neurology at the University of Southern California, Los Angeles, and a designated discussant for the report.

The result “was rather encouraging. I was a little surprised” by the findings, commented Chrystie M. Ballantyne, MD, professor and director of the Center for Cardiometabolic Disease Prevention at Baylor College of Medicine, Houston, also a discussant.

The results “don’t mean that no one benefits from aspirin. Perhaps certain people at risk would benefit from dementia protection. It’s an open question,” commented Erin D. Michos, MD, director of Women’s Cardiovascular Health at Johns Hopkins Medicine, Baltimore.

Evidence against routine, widespread primary prevention with aspirin

ASCEND had the primary goal of assessing a daily, 100-mg aspirin dose for its safety and efficacy for preventing vascular events such as MIs and ischemic strokes in 15,480 people with diabetes who were at least 40 years old at enrollment and had no history of cardiovascular disease. The main results came out in 2018 and showed that while aspirin produced a significant benefit by reducing thrombotic events, it also resulted in significantly more major bleeding events compared with placebo, and overall the magnitude of benefit roughly matched magnitude of risk.

These findings, along with similar results from two other high-profile aspirin studies reported at about the same time (ASPREE, and ARRIVE), led to recommendations from groups like the U.S. Preventive Services Task Force and from the American College of Cardiology and American Heart Association that caution against widespread, routine aspirin use for primary prevention of atherosclerotic cardiovascular disease events in most adults.

The groups instead endorsed a tailored strategy of targeting aspirin to people with a higher than average risk for ischemic thrombotic events and a lower than average bleeding risk. (The most recent aspirin recommendations from the USPSTF, currently in draft form, substantially curtail aspirin’s appropriate use, eliminating it in those over age 60 years.)

However, experts and prevailing practice recommendations continue to endorse routine aspirin use for secondary prevention in patients with an established history of cardiovascular disease.

The new findings reported by Dr. Armitage came from additional analyses of dementia and cognitive impairment overlaid on the main ASCEND outcome analyses. ASCEND actively treated and followed study participants for an average of 7.4 years, then researchers tracked further dementia outcomes based on medical-record entries for an average of another 1.8 years.

ASCEND received partial funding or support from Abbott, Bayer, Mylan, and Solvay. Dr. Armitage had no disclosures. Dr. Towfighi, Dr. Khera, and Dr. Michos had no disclosures. Dr. Ballantyne has had financial relationships with numerous companies.

mzoler@mdedge.com

A regimen of daily, low-dose aspirin failed to produce a significant reduction in the incidence of dementia or cognitive impairment in ASCEND, a randomized, multicenter trial with more than 15,000 people with diabetes followed for an average of more than 9 years, but the results hinted at enough of a benefit to warrant further study, some experts said.

jimdeli/Fotolia

A second metric used a broader outcome definition that tracked EHR entries for not only dementia but also diagnoses of cognitive impairment, delirium, confusion, prescription of dementia medications, and referral to a memory clinic or geriatric psychiatry. The third assessment was a cognitive-function test given to participants at the end of follow-up, but only 58% of enrolled participants completed this part of the study, and it’s also possible that some subjects missed this assessment because of dementia onset. These limitations hamper clear interpretation of this third metric, Dr. Armitage said.

The main findings for the other two, more reliable measures of incident dementia or cognitive deterioration showed a nonsignificant 9% relative risk reduction linked with aspirin use compared with placebo for the more inclusive endpoint, and a nonsignificant 11% relative risk reduction with aspirin using the narrow definition for dementia only, she reported. The third method, a directly administered assessment of dementia and cognition, also showed a small, nonsignificant effect from daily aspirin use relative to placebo.

Results can’t rule out modest aspirin effect

Dr. Armitage highlighted that the two more reliable measures both appeared to rule out risk for neurologic harm from aspirin because the upper limit of the 95% confidence interval for relative effect reached only 1.02 using the broad outcomes, and 1.06 for the narrower endpoint of dementia only. On the other hand, focus on the low end of the 95% confidence interval suggested potentially meaningful benefits, with a possible reduction by aspirin in events relative to placebo of as much as 19% by the broad outcome definition and by 25% with the narrow definition.

“Even if it was only a 15% relative risk reduction, that would be important,” given the high dementia incidence worldwide, Dr. Armitage said during a press briefing. “It’s entirely possible, with our results, that a modest benefit exists.”

This take on the findings won some support. Further studies with more people, longer follow-up, and perhaps enrolling a more selected, higher risk cohort may better address potential neurologic benefit from aspirin, suggested Amytis Towfighi, MD, a stroke neurologist and professor of neurology at the University of Southern California, Los Angeles, and a designated discussant for the report.

The result “was rather encouraging. I was a little surprised” by the findings, commented Chrystie M. Ballantyne, MD, professor and director of the Center for Cardiometabolic Disease Prevention at Baylor College of Medicine, Houston, also a discussant.

The results “don’t mean that no one benefits from aspirin. Perhaps certain people at risk would benefit from dementia protection. It’s an open question,” commented Erin D. Michos, MD, director of Women’s Cardiovascular Health at Johns Hopkins Medicine, Baltimore.

Evidence against routine, widespread primary prevention with aspirin

ASCEND had the primary goal of assessing a daily, 100-mg aspirin dose for its safety and efficacy for preventing vascular events such as MIs and ischemic strokes in 15,480 people with diabetes who were at least 40 years old at enrollment and had no history of cardiovascular disease. The main results came out in 2018 and showed that while aspirin produced a significant benefit by reducing thrombotic events, it also resulted in significantly more major bleeding events compared with placebo, and overall the magnitude of benefit roughly matched magnitude of risk.

These findings, along with similar results from two other high-profile aspirin studies reported at about the same time (ASPREE, and ARRIVE), led to recommendations from groups like the U.S. Preventive Services Task Force and from the American College of Cardiology and American Heart Association that caution against widespread, routine aspirin use for primary prevention of atherosclerotic cardiovascular disease events in most adults.

The groups instead endorsed a tailored strategy of targeting aspirin to people with a higher than average risk for ischemic thrombotic events and a lower than average bleeding risk. (The most recent aspirin recommendations from the USPSTF, currently in draft form, substantially curtail aspirin’s appropriate use, eliminating it in those over age 60 years.)

However, experts and prevailing practice recommendations continue to endorse routine aspirin use for secondary prevention in patients with an established history of cardiovascular disease.

The new findings reported by Dr. Armitage came from additional analyses of dementia and cognitive impairment overlaid on the main ASCEND outcome analyses. ASCEND actively treated and followed study participants for an average of 7.4 years, then researchers tracked further dementia outcomes based on medical-record entries for an average of another 1.8 years.

ASCEND received partial funding or support from Abbott, Bayer, Mylan, and Solvay. Dr. Armitage had no disclosures. Dr. Towfighi, Dr. Khera, and Dr. Michos had no disclosures. Dr. Ballantyne has had financial relationships with numerous companies.

mzoler@mdedge.com

A regimen of daily, low-dose aspirin failed to produce a significant reduction in the incidence of dementia or cognitive impairment in ASCEND, a randomized, multicenter trial with more than 15,000 people with diabetes followed for an average of more than 9 years, but the results hinted at enough of a benefit to warrant further study, some experts said.

jimdeli/Fotolia

A second metric used a broader outcome definition that tracked EHR entries for not only dementia but also diagnoses of cognitive impairment, delirium, confusion, prescription of dementia medications, and referral to a memory clinic or geriatric psychiatry. The third assessment was a cognitive-function test given to participants at the end of follow-up, but only 58% of enrolled participants completed this part of the study, and it’s also possible that some subjects missed this assessment because of dementia onset. These limitations hamper clear interpretation of this third metric, Dr. Armitage said.

The main findings for the other two, more reliable measures of incident dementia or cognitive deterioration showed a nonsignificant 9% relative risk reduction linked with aspirin use compared with placebo for the more inclusive endpoint, and a nonsignificant 11% relative risk reduction with aspirin using the narrow definition for dementia only, she reported. The third method, a directly administered assessment of dementia and cognition, also showed a small, nonsignificant effect from daily aspirin use relative to placebo.

Results can’t rule out modest aspirin effect

Dr. Armitage highlighted that the two more reliable measures both appeared to rule out risk for neurologic harm from aspirin because the upper limit of the 95% confidence interval for relative effect reached only 1.02 using the broad outcomes, and 1.06 for the narrower endpoint of dementia only. On the other hand, focus on the low end of the 95% confidence interval suggested potentially meaningful benefits, with a possible reduction by aspirin in events relative to placebo of as much as 19% by the broad outcome definition and by 25% with the narrow definition.

“Even if it was only a 15% relative risk reduction, that would be important,” given the high dementia incidence worldwide, Dr. Armitage said during a press briefing. “It’s entirely possible, with our results, that a modest benefit exists.”

This take on the findings won some support. Further studies with more people, longer follow-up, and perhaps enrolling a more selected, higher risk cohort may better address potential neurologic benefit from aspirin, suggested Amytis Towfighi, MD, a stroke neurologist and professor of neurology at the University of Southern California, Los Angeles, and a designated discussant for the report.

The result “was rather encouraging. I was a little surprised” by the findings, commented Chrystie M. Ballantyne, MD, professor and director of the Center for Cardiometabolic Disease Prevention at Baylor College of Medicine, Houston, also a discussant.

The results “don’t mean that no one benefits from aspirin. Perhaps certain people at risk would benefit from dementia protection. It’s an open question,” commented Erin D. Michos, MD, director of Women’s Cardiovascular Health at Johns Hopkins Medicine, Baltimore.

Evidence against routine, widespread primary prevention with aspirin

ASCEND had the primary goal of assessing a daily, 100-mg aspirin dose for its safety and efficacy for preventing vascular events such as MIs and ischemic strokes in 15,480 people with diabetes who were at least 40 years old at enrollment and had no history of cardiovascular disease. The main results came out in 2018 and showed that while aspirin produced a significant benefit by reducing thrombotic events, it also resulted in significantly more major bleeding events compared with placebo, and overall the magnitude of benefit roughly matched magnitude of risk.

These findings, along with similar results from two other high-profile aspirin studies reported at about the same time (ASPREE, and ARRIVE), led to recommendations from groups like the U.S. Preventive Services Task Force and from the American College of Cardiology and American Heart Association that caution against widespread, routine aspirin use for primary prevention of atherosclerotic cardiovascular disease events in most adults.

The groups instead endorsed a tailored strategy of targeting aspirin to people with a higher than average risk for ischemic thrombotic events and a lower than average bleeding risk. (The most recent aspirin recommendations from the USPSTF, currently in draft form, substantially curtail aspirin’s appropriate use, eliminating it in those over age 60 years.)

However, experts and prevailing practice recommendations continue to endorse routine aspirin use for secondary prevention in patients with an established history of cardiovascular disease.

The new findings reported by Dr. Armitage came from additional analyses of dementia and cognitive impairment overlaid on the main ASCEND outcome analyses. ASCEND actively treated and followed study participants for an average of 7.4 years, then researchers tracked further dementia outcomes based on medical-record entries for an average of another 1.8 years.

ASCEND received partial funding or support from Abbott, Bayer, Mylan, and Solvay. Dr. Armitage had no disclosures. Dr. Towfighi, Dr. Khera, and Dr. Michos had no disclosures. Dr. Ballantyne has had financial relationships with numerous companies.

mzoler@mdedge.com

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

On Nov. 12, president Joe Biden said he will nominate Robert Califf, MD, to be commissioner of the U.S. Food and Drug Administration, the top U.S. regulator of drugs and medical devices.

Dr. Califf, a cardiologist, served as FDA chief in the Obama administration, leading the agency from Feb. 2016 to Jan. 2017.

The coming nomination ends nearly 11 months of speculation over Mr. Biden’s pick to the lead the agency during the ongoing pandemic. Janet Woodcock, MD, an FDA veteran, has been serving as acting commissioner. The White House faced a Tuesday deadline to make a nomination or see Dr. Woodcock’s tenure as acting chief expire under federal law.

The initial reaction to the idea of Dr. Califf’s return to the FDA drew mixed reactions.

The nonprofit watchdog Public Citizen issued a statement about its opposition to the potential nomination of Dr. Califf. Michael Carome, MD, director of Public Citizen’s Health Research Group, said the United States “desperately needs an FDA leader who will reverse the decades-long trend in which the agency’s relationship with the pharmaceutical and medical-device industries has grown dangerously cozier – resulting in regulatory capture of the agency by industry.”

But the idea of Dr. Califf returning to the FDA pleased Harlan Krumholz, MD, a cardiologist who has been a leader in outcomes research.

Dr. Krumholz tweeted that the Biden administration likely was testing the reaction to a possible Dr. Califf nomination before making it official. “I realize that this is being floated and not officially announced ... but the nomination of [Califf] just makes so much sense,” Dr. Krumholz tweeted. Dr. Califf’s “expertise as a researcher, policymaker, clinician are unparalleled. In a time of partisanship, he should be a slam-dunk confirmation.”

Dr. Califf’s 2016 Senate confirmation process was marked by dissent from several Democrats who questioned his ties to industry. But the chamber voted 89-4 to confirm him.

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

On Nov. 12, president Joe Biden said he will nominate Robert Califf, MD, to be commissioner of the U.S. Food and Drug Administration, the top U.S. regulator of drugs and medical devices.

Dr. Califf, a cardiologist, served as FDA chief in the Obama administration, leading the agency from Feb. 2016 to Jan. 2017.

The coming nomination ends nearly 11 months of speculation over Mr. Biden’s pick to the lead the agency during the ongoing pandemic. Janet Woodcock, MD, an FDA veteran, has been serving as acting commissioner. The White House faced a Tuesday deadline to make a nomination or see Dr. Woodcock’s tenure as acting chief expire under federal law.

The initial reaction to the idea of Dr. Califf’s return to the FDA drew mixed reactions.

The nonprofit watchdog Public Citizen issued a statement about its opposition to the potential nomination of Dr. Califf. Michael Carome, MD, director of Public Citizen’s Health Research Group, said the United States “desperately needs an FDA leader who will reverse the decades-long trend in which the agency’s relationship with the pharmaceutical and medical-device industries has grown dangerously cozier – resulting in regulatory capture of the agency by industry.”

But the idea of Dr. Califf returning to the FDA pleased Harlan Krumholz, MD, a cardiologist who has been a leader in outcomes research.

Dr. Krumholz tweeted that the Biden administration likely was testing the reaction to a possible Dr. Califf nomination before making it official. “I realize that this is being floated and not officially announced ... but the nomination of [Califf] just makes so much sense,” Dr. Krumholz tweeted. Dr. Califf’s “expertise as a researcher, policymaker, clinician are unparalleled. In a time of partisanship, he should be a slam-dunk confirmation.”

Dr. Califf’s 2016 Senate confirmation process was marked by dissent from several Democrats who questioned his ties to industry. But the chamber voted 89-4 to confirm him.

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

On Nov. 12, president Joe Biden said he will nominate Robert Califf, MD, to be commissioner of the U.S. Food and Drug Administration, the top U.S. regulator of drugs and medical devices.

Dr. Califf, a cardiologist, served as FDA chief in the Obama administration, leading the agency from Feb. 2016 to Jan. 2017.

The coming nomination ends nearly 11 months of speculation over Mr. Biden’s pick to the lead the agency during the ongoing pandemic. Janet Woodcock, MD, an FDA veteran, has been serving as acting commissioner. The White House faced a Tuesday deadline to make a nomination or see Dr. Woodcock’s tenure as acting chief expire under federal law.

The initial reaction to the idea of Dr. Califf’s return to the FDA drew mixed reactions.

The nonprofit watchdog Public Citizen issued a statement about its opposition to the potential nomination of Dr. Califf. Michael Carome, MD, director of Public Citizen’s Health Research Group, said the United States “desperately needs an FDA leader who will reverse the decades-long trend in which the agency’s relationship with the pharmaceutical and medical-device industries has grown dangerously cozier – resulting in regulatory capture of the agency by industry.”

But the idea of Dr. Califf returning to the FDA pleased Harlan Krumholz, MD, a cardiologist who has been a leader in outcomes research.

Dr. Krumholz tweeted that the Biden administration likely was testing the reaction to a possible Dr. Califf nomination before making it official. “I realize that this is being floated and not officially announced ... but the nomination of [Califf] just makes so much sense,” Dr. Krumholz tweeted. Dr. Califf’s “expertise as a researcher, policymaker, clinician are unparalleled. In a time of partisanship, he should be a slam-dunk confirmation.”

Dr. Califf’s 2016 Senate confirmation process was marked by dissent from several Democrats who questioned his ties to industry. But the chamber voted 89-4 to confirm him.

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

Higher intake of vegetable fats from foods such as olive oil and nuts is associated with a lower risk for stroke, whereas people who eat more animal fats, especially processed red meats, may have a higher stroke risk, observational findings suggest.

camij/thinkstockphotos.com

In a study of more than 117,000 health professionals who were followed for 27 years, those whose diet was in the highest quintile for intake of vegetable fat had a 12% lower risk for stroke, compared with those who consumed the least amount of vegetable fats.

Conversely, having the highest intake of animal fat from nondairy sources was associated with a 16% increased risk of stroke.

Fenglei Wang, PhD, presented these results at the American Heart Association scientific sessions.

“Our findings support the Dietary Guidelines for Americans and dietary recommendations by AHA,” Dr. Wang, a postdoctoral fellow in the department of nutrition at Harvard University’s T.H. Chan School of Public Health in Boston, told this news organization.

“The main sources of vegetable fat have a large overlap with polyunsaturated fat, such as vegetable oils, nuts, walnuts, and peanut butter,” Dr. Wang noted, adding that fish, especially fatty fish, is a main source of polyunsaturated fat and is recommended for cardiovascular health.

“We would recommend that people reduce consumption of red and processed meat, minimize fatty parts of unprocessed meat if consumed, and replace lard or tallow (beef fat) with nontropical vegetable oils, such as olive oil, corn, or soybean oils in cooking, to lower their stroke risk,” she said.

Moreover, although the results from this study of dietary fat are informative, Dr. Wang continued, “there are other dietary factors (fruits, vegetables, salt, alcohol, et cetera), and lifestyle factors (physical activity, smoking, et cetera), that are associated with stroke risk and worthy of attention as well.”

“Many processed meats are high in salt and saturated fat, and low in vegetable fat,” Alice H. Lichtenstein, DSc, an AHA spokesperson who was not involved with this research, noted in a press release.

“Research shows that replacing processed meat with other protein sources, particularly plant sources, is associated with lower death rates,” added Dr. Lichtenstein, the Stanley N. Gershoff professor of nutrition science and policy at Tufts University in Boston, and lead author of the AHA’s 2021 scientific statement, Dietary Guidance to Improve Cardiovascular Health.

“Key features of a heart-healthy diet pattern,” she summarized, “are to balance calorie intake with calorie needs to achieve and maintain a healthy weight; choose whole grains, lean and plant-based protein, and a variety of fruits and vegetables; limit salt, sugar, animal fat, processed foods, and alcohol; and apply this guidance regardless of where the food is prepared or consumed.”
 

Replace processed meat with plant proteins

The focus on stroke in this study “is important” because, traditionally, studies of diet and cardiovascular health have focused on coronary heart disease, Andrew Mente, PhD, who also was not involved in this research, said in an email to this news organization.

“Overall, the take-home message from the study is that replacing processed meat with plant sources of protein in the diet is probably beneficial,” Dr. Mente, associate professor, health research methods, evidence, and impact, Faculty of Health Sciences, McMaster University, Hamilton, Ont., said.

The finding that people who ate the most vegetable fat had a modest 12% lower risk of stroke than those who ate the least vegetable fat “points to protective effects of foods like seeds, nuts, vegetables, and olive oil, which has been shown previously,” he continued.

The highest quintile of total red meat intake was associated with an 8% higher risk for stroke, but this was driven mainly by processed red meat (which was associated with a 12% higher risk for stroke). These findings are “generally consistent with cohort studies showing that processed meat, as with most highly processed foods for that matter, are associated with an increased risk of cardiovascular events,” Dr. Mente noted.

“Surprisingly, dairy products (such as cheese, butter, or milk) in the study were not connected with the risk of stroke,” he added. This finding differs from results of meta-analyses of multiple cohort studies of dairy intake and stroke and the recent large international PURE study, which showed that dairy intake was associated with a lower risk for stroke.

“What is needed to move the field forward,” according to Dr. Mente, “is to employ new methods that use cutting-edge technology to study nutritional biomarkers and health outcomes.”

“When dealing with modest associations as usually encountered in nutrition, it is a challenge to make causal connections based on dietary questionnaires, which are fraught with measurement error,” he added. “The use of novel methods is where the field is headed.”
 

Total dietary fat, different types, and different food sources

Dr. Wang and colleagues investigated how total dietary fat, different types of fat, and fats from different foods were associated with incident stroke in 73,867 women in the 1984-2016 Nurses’ Health Study and 43,269 men who participated in the 1986-2016 Health Professionals Follow-up Study.

The participants had an average age of 50 years, 63% were women, and 97% were White. They replied to food-frequency questionnaires every 4 years.

Total red meat included beef, pork, or lamb (as a main dish or in sandwiches or mixed dishes) as well as processed red meats (such as bacon, sausage, bologna, hot dogs, and salami).

Animal fat sources included meat, beef tallow, lard, and full-fat dairy products, such as full-fat milk and cheese.

The median percentage of total daily calories from different sources of fat ranged from 10% to 20% for vegetable fat, 3% to 10% for dairy fat, and 7% to 17% for nondairy animal fat (for lowest to highest quintiles).

The median percentage of total daily calories from different types of fat ranged from 5% to 8% for polyunsaturated fat, 4% to 7% for n-6 polyunsaturated fat, 9% to 15% for monounsaturated fat, 8% to 14% for saturated fat, and 1% to 2% for trans fat.

During follow-up, there were 6,189 incident strokes, including 2,967 ischemic strokes and 814 hemorrhagic strokes.

The researchers found that intake in the highest quintile of vegetable fat was associated with a lower risk for total stroke, compared with the lowest quintile (hazard ratio, 0.88; 95% confidence interval, 0.81-0.96; P for trend < .001).

Similarly, the highest intake of polyunsaturated fat was also associated with lower total stroke (HR, 0.88; 95% CI, 0.80-0.96; P for trend = .002). 

Highest intake of nondairy animal fat, however, was associated with an increased risk for total stroke (HR, 1.16; 95% CI, 1.05-1.29; P for trend < .001). They observed “similar associations” for ischemic stroke, but the only positive association for nondairy animal fat was with hemorrhagic stroke, the abstract notes.   

The risk for stroke was lower by 9% per serving per day for vegetable oil but increased by 8% and 12%, respectively, per serving of total red meat or processed red meat.

The association for vegetable oil was attenuated after adjustment for vegetable fat or polyunsaturated fat, whereas adjustment for nondairy animal fat rendered the association for total red meat and processed red meat nonsignificant. 

The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Wang has no relevant financial disclosures. Dr. Mente has received research funding from the Dairy Farmers of Canada and the National Dairy Council to analyze data on dairy consumption and health outcomes in the PURE study, which is funded by the Population Health Research Institute, Hamilton Health Sciences Research Institute, and more than 70 other sources (government and pharmaceutical).

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

Higher intake of vegetable fats from foods such as olive oil and nuts is associated with a lower risk for stroke, whereas people who eat more animal fats, especially processed red meats, may have a higher stroke risk, observational findings suggest.

camij/thinkstockphotos.com

In a study of more than 117,000 health professionals who were followed for 27 years, those whose diet was in the highest quintile for intake of vegetable fat had a 12% lower risk for stroke, compared with those who consumed the least amount of vegetable fats.

Conversely, having the highest intake of animal fat from nondairy sources was associated with a 16% increased risk of stroke.

Fenglei Wang, PhD, presented these results at the American Heart Association scientific sessions.

“Our findings support the Dietary Guidelines for Americans and dietary recommendations by AHA,” Dr. Wang, a postdoctoral fellow in the department of nutrition at Harvard University’s T.H. Chan School of Public Health in Boston, told this news organization.

“The main sources of vegetable fat have a large overlap with polyunsaturated fat, such as vegetable oils, nuts, walnuts, and peanut butter,” Dr. Wang noted, adding that fish, especially fatty fish, is a main source of polyunsaturated fat and is recommended for cardiovascular health.

“We would recommend that people reduce consumption of red and processed meat, minimize fatty parts of unprocessed meat if consumed, and replace lard or tallow (beef fat) with nontropical vegetable oils, such as olive oil, corn, or soybean oils in cooking, to lower their stroke risk,” she said.

Moreover, although the results from this study of dietary fat are informative, Dr. Wang continued, “there are other dietary factors (fruits, vegetables, salt, alcohol, et cetera), and lifestyle factors (physical activity, smoking, et cetera), that are associated with stroke risk and worthy of attention as well.”

“Many processed meats are high in salt and saturated fat, and low in vegetable fat,” Alice H. Lichtenstein, DSc, an AHA spokesperson who was not involved with this research, noted in a press release.

“Research shows that replacing processed meat with other protein sources, particularly plant sources, is associated with lower death rates,” added Dr. Lichtenstein, the Stanley N. Gershoff professor of nutrition science and policy at Tufts University in Boston, and lead author of the AHA’s 2021 scientific statement, Dietary Guidance to Improve Cardiovascular Health.

“Key features of a heart-healthy diet pattern,” she summarized, “are to balance calorie intake with calorie needs to achieve and maintain a healthy weight; choose whole grains, lean and plant-based protein, and a variety of fruits and vegetables; limit salt, sugar, animal fat, processed foods, and alcohol; and apply this guidance regardless of where the food is prepared or consumed.”
 

Replace processed meat with plant proteins

The focus on stroke in this study “is important” because, traditionally, studies of diet and cardiovascular health have focused on coronary heart disease, Andrew Mente, PhD, who also was not involved in this research, said in an email to this news organization.

“Overall, the take-home message from the study is that replacing processed meat with plant sources of protein in the diet is probably beneficial,” Dr. Mente, associate professor, health research methods, evidence, and impact, Faculty of Health Sciences, McMaster University, Hamilton, Ont., said.

The finding that people who ate the most vegetable fat had a modest 12% lower risk of stroke than those who ate the least vegetable fat “points to protective effects of foods like seeds, nuts, vegetables, and olive oil, which has been shown previously,” he continued.

The highest quintile of total red meat intake was associated with an 8% higher risk for stroke, but this was driven mainly by processed red meat (which was associated with a 12% higher risk for stroke). These findings are “generally consistent with cohort studies showing that processed meat, as with most highly processed foods for that matter, are associated with an increased risk of cardiovascular events,” Dr. Mente noted.

“Surprisingly, dairy products (such as cheese, butter, or milk) in the study were not connected with the risk of stroke,” he added. This finding differs from results of meta-analyses of multiple cohort studies of dairy intake and stroke and the recent large international PURE study, which showed that dairy intake was associated with a lower risk for stroke.

“What is needed to move the field forward,” according to Dr. Mente, “is to employ new methods that use cutting-edge technology to study nutritional biomarkers and health outcomes.”

“When dealing with modest associations as usually encountered in nutrition, it is a challenge to make causal connections based on dietary questionnaires, which are fraught with measurement error,” he added. “The use of novel methods is where the field is headed.”
 

Total dietary fat, different types, and different food sources

Dr. Wang and colleagues investigated how total dietary fat, different types of fat, and fats from different foods were associated with incident stroke in 73,867 women in the 1984-2016 Nurses’ Health Study and 43,269 men who participated in the 1986-2016 Health Professionals Follow-up Study.

The participants had an average age of 50 years, 63% were women, and 97% were White. They replied to food-frequency questionnaires every 4 years.

Total red meat included beef, pork, or lamb (as a main dish or in sandwiches or mixed dishes) as well as processed red meats (such as bacon, sausage, bologna, hot dogs, and salami).

Animal fat sources included meat, beef tallow, lard, and full-fat dairy products, such as full-fat milk and cheese.

The median percentage of total daily calories from different sources of fat ranged from 10% to 20% for vegetable fat, 3% to 10% for dairy fat, and 7% to 17% for nondairy animal fat (for lowest to highest quintiles).

The median percentage of total daily calories from different types of fat ranged from 5% to 8% for polyunsaturated fat, 4% to 7% for n-6 polyunsaturated fat, 9% to 15% for monounsaturated fat, 8% to 14% for saturated fat, and 1% to 2% for trans fat.

During follow-up, there were 6,189 incident strokes, including 2,967 ischemic strokes and 814 hemorrhagic strokes.

The researchers found that intake in the highest quintile of vegetable fat was associated with a lower risk for total stroke, compared with the lowest quintile (hazard ratio, 0.88; 95% confidence interval, 0.81-0.96; P for trend < .001).

Similarly, the highest intake of polyunsaturated fat was also associated with lower total stroke (HR, 0.88; 95% CI, 0.80-0.96; P for trend = .002). 

Highest intake of nondairy animal fat, however, was associated with an increased risk for total stroke (HR, 1.16; 95% CI, 1.05-1.29; P for trend < .001). They observed “similar associations” for ischemic stroke, but the only positive association for nondairy animal fat was with hemorrhagic stroke, the abstract notes.   

The risk for stroke was lower by 9% per serving per day for vegetable oil but increased by 8% and 12%, respectively, per serving of total red meat or processed red meat.

The association for vegetable oil was attenuated after adjustment for vegetable fat or polyunsaturated fat, whereas adjustment for nondairy animal fat rendered the association for total red meat and processed red meat nonsignificant. 

The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Wang has no relevant financial disclosures. Dr. Mente has received research funding from the Dairy Farmers of Canada and the National Dairy Council to analyze data on dairy consumption and health outcomes in the PURE study, which is funded by the Population Health Research Institute, Hamilton Health Sciences Research Institute, and more than 70 other sources (government and pharmaceutical).

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

Higher intake of vegetable fats from foods such as olive oil and nuts is associated with a lower risk for stroke, whereas people who eat more animal fats, especially processed red meats, may have a higher stroke risk, observational findings suggest.

camij/thinkstockphotos.com

In a study of more than 117,000 health professionals who were followed for 27 years, those whose diet was in the highest quintile for intake of vegetable fat had a 12% lower risk for stroke, compared with those who consumed the least amount of vegetable fats.

Conversely, having the highest intake of animal fat from nondairy sources was associated with a 16% increased risk of stroke.

Fenglei Wang, PhD, presented these results at the American Heart Association scientific sessions.

“Our findings support the Dietary Guidelines for Americans and dietary recommendations by AHA,” Dr. Wang, a postdoctoral fellow in the department of nutrition at Harvard University’s T.H. Chan School of Public Health in Boston, told this news organization.

“The main sources of vegetable fat have a large overlap with polyunsaturated fat, such as vegetable oils, nuts, walnuts, and peanut butter,” Dr. Wang noted, adding that fish, especially fatty fish, is a main source of polyunsaturated fat and is recommended for cardiovascular health.

“We would recommend that people reduce consumption of red and processed meat, minimize fatty parts of unprocessed meat if consumed, and replace lard or tallow (beef fat) with nontropical vegetable oils, such as olive oil, corn, or soybean oils in cooking, to lower their stroke risk,” she said.

Moreover, although the results from this study of dietary fat are informative, Dr. Wang continued, “there are other dietary factors (fruits, vegetables, salt, alcohol, et cetera), and lifestyle factors (physical activity, smoking, et cetera), that are associated with stroke risk and worthy of attention as well.”

“Many processed meats are high in salt and saturated fat, and low in vegetable fat,” Alice H. Lichtenstein, DSc, an AHA spokesperson who was not involved with this research, noted in a press release.

“Research shows that replacing processed meat with other protein sources, particularly plant sources, is associated with lower death rates,” added Dr. Lichtenstein, the Stanley N. Gershoff professor of nutrition science and policy at Tufts University in Boston, and lead author of the AHA’s 2021 scientific statement, Dietary Guidance to Improve Cardiovascular Health.

“Key features of a heart-healthy diet pattern,” she summarized, “are to balance calorie intake with calorie needs to achieve and maintain a healthy weight; choose whole grains, lean and plant-based protein, and a variety of fruits and vegetables; limit salt, sugar, animal fat, processed foods, and alcohol; and apply this guidance regardless of where the food is prepared or consumed.”
 

Replace processed meat with plant proteins

The focus on stroke in this study “is important” because, traditionally, studies of diet and cardiovascular health have focused on coronary heart disease, Andrew Mente, PhD, who also was not involved in this research, said in an email to this news organization.

“Overall, the take-home message from the study is that replacing processed meat with plant sources of protein in the diet is probably beneficial,” Dr. Mente, associate professor, health research methods, evidence, and impact, Faculty of Health Sciences, McMaster University, Hamilton, Ont., said.

The finding that people who ate the most vegetable fat had a modest 12% lower risk of stroke than those who ate the least vegetable fat “points to protective effects of foods like seeds, nuts, vegetables, and olive oil, which has been shown previously,” he continued.

The highest quintile of total red meat intake was associated with an 8% higher risk for stroke, but this was driven mainly by processed red meat (which was associated with a 12% higher risk for stroke). These findings are “generally consistent with cohort studies showing that processed meat, as with most highly processed foods for that matter, are associated with an increased risk of cardiovascular events,” Dr. Mente noted.

“Surprisingly, dairy products (such as cheese, butter, or milk) in the study were not connected with the risk of stroke,” he added. This finding differs from results of meta-analyses of multiple cohort studies of dairy intake and stroke and the recent large international PURE study, which showed that dairy intake was associated with a lower risk for stroke.

“What is needed to move the field forward,” according to Dr. Mente, “is to employ new methods that use cutting-edge technology to study nutritional biomarkers and health outcomes.”

“When dealing with modest associations as usually encountered in nutrition, it is a challenge to make causal connections based on dietary questionnaires, which are fraught with measurement error,” he added. “The use of novel methods is where the field is headed.”
 

Total dietary fat, different types, and different food sources

Dr. Wang and colleagues investigated how total dietary fat, different types of fat, and fats from different foods were associated with incident stroke in 73,867 women in the 1984-2016 Nurses’ Health Study and 43,269 men who participated in the 1986-2016 Health Professionals Follow-up Study.

The participants had an average age of 50 years, 63% were women, and 97% were White. They replied to food-frequency questionnaires every 4 years.

Total red meat included beef, pork, or lamb (as a main dish or in sandwiches or mixed dishes) as well as processed red meats (such as bacon, sausage, bologna, hot dogs, and salami).

Animal fat sources included meat, beef tallow, lard, and full-fat dairy products, such as full-fat milk and cheese.

The median percentage of total daily calories from different sources of fat ranged from 10% to 20% for vegetable fat, 3% to 10% for dairy fat, and 7% to 17% for nondairy animal fat (for lowest to highest quintiles).

The median percentage of total daily calories from different types of fat ranged from 5% to 8% for polyunsaturated fat, 4% to 7% for n-6 polyunsaturated fat, 9% to 15% for monounsaturated fat, 8% to 14% for saturated fat, and 1% to 2% for trans fat.

During follow-up, there were 6,189 incident strokes, including 2,967 ischemic strokes and 814 hemorrhagic strokes.

The researchers found that intake in the highest quintile of vegetable fat was associated with a lower risk for total stroke, compared with the lowest quintile (hazard ratio, 0.88; 95% confidence interval, 0.81-0.96; P for trend < .001).

Similarly, the highest intake of polyunsaturated fat was also associated with lower total stroke (HR, 0.88; 95% CI, 0.80-0.96; P for trend = .002). 

Highest intake of nondairy animal fat, however, was associated with an increased risk for total stroke (HR, 1.16; 95% CI, 1.05-1.29; P for trend < .001). They observed “similar associations” for ischemic stroke, but the only positive association for nondairy animal fat was with hemorrhagic stroke, the abstract notes.   

The risk for stroke was lower by 9% per serving per day for vegetable oil but increased by 8% and 12%, respectively, per serving of total red meat or processed red meat.

The association for vegetable oil was attenuated after adjustment for vegetable fat or polyunsaturated fat, whereas adjustment for nondairy animal fat rendered the association for total red meat and processed red meat nonsignificant. 

The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Wang has no relevant financial disclosures. Dr. Mente has received research funding from the Dairy Farmers of Canada and the National Dairy Council to analyze data on dairy consumption and health outcomes in the PURE study, which is funded by the Population Health Research Institute, Hamilton Health Sciences Research Institute, and more than 70 other sources (government and pharmaceutical).

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

In large-vessel occlusion stroke, results of a randomized trial failed to show noninferiority of direct mechanical thrombectomy using the Solitaire device to the combination of intravenous (IV) thrombolysis plus mechanical thrombectomy.

In the prospective, multicenter trial, the rate of good functional outcome was 57% for patients who underwent direct thrombectomy and 65% among patients who received IV thrombolysis before undergoing thrombectomy. This result failed to demonstrate noninferiority of direct mechanical thrombectomy compared to combination therapy, the researchers conclude.

“Good outcome was high in both treatment arms, with the point estimate in favor of the bridging cohort,” said lead investigator Urs Fischer, MD, co-chair of the stroke center at Inselspital, Bern University Hospital, Switzerland, during his presentation. “Postinterventional reperfusion was very high in both treatment arms and higher in patients with bridging thrombolysis, compared to direct mechanical thrombectomy.”

The findings were presented at the 13th World Stroke Congress (WSC) 2021.
 

Two views of thrombolysis

The value of bridging thrombolysis for patients who undergo mechanical thrombectomy is a matter of debate. One argument is that, for patients with large-vessel occlusion, IV thrombolysis may improve reperfusion before and after thrombectomy and yield better clinical outcomes. The opposing argument is that bridging thrombolysis may increase the risk for distal emboli, delay mechanical thrombectomy, and increase the rate of hemorrhage.

The researchers conducted the SWIFT DIRECT trial to investigate this question. They enrolled patients with acute ischemic stroke due to occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery.

The trial was conducted at 48 sites in seven European countries and Canada. The investigators randomly assigned patients to receive IV alteplase (0.9 mg/kg) plus mechanical thrombectomy with the Solitaire device or to receive direct mechanical thrombectomy with the same device. Treatment was open label, but the assessment of endpoints was blinded.

Investigators assigned 423 patients to treatment, and 408 were included in the full analysis set. Of this group, 201 participants received direct mechanical thrombectomy, and 207 received IV thrombolysis plus thrombectomy. There were three crossovers in each treatment arm.

The primary outcome was functional independence, defined as a Modified Rankin Scale (mRS) score of 0-2, at 90 days. Secondary outcomes included mortality at 90 days, mRS shift, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, successful reperfusion, and symptomatic and asymptomatic intracranial hemorrhage (ICH).
 

Noninferiority not demonstrated

At baseline, patient characteristics were well balanced between the treatment groups. The median age of the patients was 72 years, and about 50% of participants were women. The median NIHSS score was 17 in both arms.

Approximately 57% of patients who underwent direct thrombectomy and 65% of those who received IV thrombolysis plus thrombectomy were functionally independent at 90 days, the primary outcome.

In addition, the researchers found no difference in mRS shift, mortality at 90 days, or change in NIHSS score at 24 hours. Postinterventional reperfusion was very high in both arms and was higher in patients who received IV tissue plasminogen activator, compared with those who received direct mechanical thrombectomy, said Dr. Fischer.

The rate of successful postinterventional reperfusion, however, was higher among patients who received thrombolysis than among those who underwent direct thrombectomy. The rate of symptomatic ICH was 1.5% in the direct thrombectomy group and 4.9% in the thrombolysis-plus-thrombectomy group.
 

New endpoints needed?

The investigators used noninferiority margins of 12%. “This question about the noninferiority margins, that’s a very tricky and difficult one in randomized clinical trials,” said Dr. Fischer. The investigators defined their margin using the 2015 HERMES data because no trials had yet compared direct mechanical thrombectomy and bridging thrombolysis at the time.

The researchers are performing a pooled analysis of all the trials that compared bridging thrombolysis with direct mechanical thrombectomy. “We are therefore looking at several margins, and I think this is the way we should look at these noninferiority margins,” said Dr. Fischer. “There’s not a clear-cut level which you can define.”

Enrollment in the trial was well balanced with respect to gender, which is not always the case in stroke studies, said Kevin Sheth, MD, professor of neurology and neurosurgery at Yale School of Medicine, New Haven, Conn., who commented on the study for this news organization.

The findings indicate that the likelihood of there being a difference between groups on this question is low, said Dr. Sheth. Both groups had large-vessel occlusion, both received thrombectomy, and both achieved reperfusion. But the higher rate of successful reperfusion in the bridging cohort was not reflected in any of the clinical endpoints that the investigators examined.

Observing a difference in this context will require very large trials or different endpoints that are more responsive to the intervention, said Dr. Sheth. “This is going to be a challenge for not just this but for any neuroprotection trial in the future,” he said.

The study was supported by Medtronic. Dr. Fischer has served as a consultant for Medtronic, Stryker, and CSL Behring. Dr. Sheth has disclosed no relevant financial relationships.

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

In large-vessel occlusion stroke, results of a randomized trial failed to show noninferiority of direct mechanical thrombectomy using the Solitaire device to the combination of intravenous (IV) thrombolysis plus mechanical thrombectomy.

In the prospective, multicenter trial, the rate of good functional outcome was 57% for patients who underwent direct thrombectomy and 65% among patients who received IV thrombolysis before undergoing thrombectomy. This result failed to demonstrate noninferiority of direct mechanical thrombectomy compared to combination therapy, the researchers conclude.

“Good outcome was high in both treatment arms, with the point estimate in favor of the bridging cohort,” said lead investigator Urs Fischer, MD, co-chair of the stroke center at Inselspital, Bern University Hospital, Switzerland, during his presentation. “Postinterventional reperfusion was very high in both treatment arms and higher in patients with bridging thrombolysis, compared to direct mechanical thrombectomy.”

The findings were presented at the 13th World Stroke Congress (WSC) 2021.
 

Two views of thrombolysis

The value of bridging thrombolysis for patients who undergo mechanical thrombectomy is a matter of debate. One argument is that, for patients with large-vessel occlusion, IV thrombolysis may improve reperfusion before and after thrombectomy and yield better clinical outcomes. The opposing argument is that bridging thrombolysis may increase the risk for distal emboli, delay mechanical thrombectomy, and increase the rate of hemorrhage.

The researchers conducted the SWIFT DIRECT trial to investigate this question. They enrolled patients with acute ischemic stroke due to occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery.

The trial was conducted at 48 sites in seven European countries and Canada. The investigators randomly assigned patients to receive IV alteplase (0.9 mg/kg) plus mechanical thrombectomy with the Solitaire device or to receive direct mechanical thrombectomy with the same device. Treatment was open label, but the assessment of endpoints was blinded.

Investigators assigned 423 patients to treatment, and 408 were included in the full analysis set. Of this group, 201 participants received direct mechanical thrombectomy, and 207 received IV thrombolysis plus thrombectomy. There were three crossovers in each treatment arm.

The primary outcome was functional independence, defined as a Modified Rankin Scale (mRS) score of 0-2, at 90 days. Secondary outcomes included mortality at 90 days, mRS shift, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, successful reperfusion, and symptomatic and asymptomatic intracranial hemorrhage (ICH).
 

Noninferiority not demonstrated

At baseline, patient characteristics were well balanced between the treatment groups. The median age of the patients was 72 years, and about 50% of participants were women. The median NIHSS score was 17 in both arms.

Approximately 57% of patients who underwent direct thrombectomy and 65% of those who received IV thrombolysis plus thrombectomy were functionally independent at 90 days, the primary outcome.

In addition, the researchers found no difference in mRS shift, mortality at 90 days, or change in NIHSS score at 24 hours. Postinterventional reperfusion was very high in both arms and was higher in patients who received IV tissue plasminogen activator, compared with those who received direct mechanical thrombectomy, said Dr. Fischer.

The rate of successful postinterventional reperfusion, however, was higher among patients who received thrombolysis than among those who underwent direct thrombectomy. The rate of symptomatic ICH was 1.5% in the direct thrombectomy group and 4.9% in the thrombolysis-plus-thrombectomy group.
 

New endpoints needed?

The investigators used noninferiority margins of 12%. “This question about the noninferiority margins, that’s a very tricky and difficult one in randomized clinical trials,” said Dr. Fischer. The investigators defined their margin using the 2015 HERMES data because no trials had yet compared direct mechanical thrombectomy and bridging thrombolysis at the time.

The researchers are performing a pooled analysis of all the trials that compared bridging thrombolysis with direct mechanical thrombectomy. “We are therefore looking at several margins, and I think this is the way we should look at these noninferiority margins,” said Dr. Fischer. “There’s not a clear-cut level which you can define.”

Enrollment in the trial was well balanced with respect to gender, which is not always the case in stroke studies, said Kevin Sheth, MD, professor of neurology and neurosurgery at Yale School of Medicine, New Haven, Conn., who commented on the study for this news organization.

The findings indicate that the likelihood of there being a difference between groups on this question is low, said Dr. Sheth. Both groups had large-vessel occlusion, both received thrombectomy, and both achieved reperfusion. But the higher rate of successful reperfusion in the bridging cohort was not reflected in any of the clinical endpoints that the investigators examined.

Observing a difference in this context will require very large trials or different endpoints that are more responsive to the intervention, said Dr. Sheth. “This is going to be a challenge for not just this but for any neuroprotection trial in the future,” he said.

The study was supported by Medtronic. Dr. Fischer has served as a consultant for Medtronic, Stryker, and CSL Behring. Dr. Sheth has disclosed no relevant financial relationships.

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

In large-vessel occlusion stroke, results of a randomized trial failed to show noninferiority of direct mechanical thrombectomy using the Solitaire device to the combination of intravenous (IV) thrombolysis plus mechanical thrombectomy.

In the prospective, multicenter trial, the rate of good functional outcome was 57% for patients who underwent direct thrombectomy and 65% among patients who received IV thrombolysis before undergoing thrombectomy. This result failed to demonstrate noninferiority of direct mechanical thrombectomy compared to combination therapy, the researchers conclude.

“Good outcome was high in both treatment arms, with the point estimate in favor of the bridging cohort,” said lead investigator Urs Fischer, MD, co-chair of the stroke center at Inselspital, Bern University Hospital, Switzerland, during his presentation. “Postinterventional reperfusion was very high in both treatment arms and higher in patients with bridging thrombolysis, compared to direct mechanical thrombectomy.”

The findings were presented at the 13th World Stroke Congress (WSC) 2021.
 

Two views of thrombolysis

The value of bridging thrombolysis for patients who undergo mechanical thrombectomy is a matter of debate. One argument is that, for patients with large-vessel occlusion, IV thrombolysis may improve reperfusion before and after thrombectomy and yield better clinical outcomes. The opposing argument is that bridging thrombolysis may increase the risk for distal emboli, delay mechanical thrombectomy, and increase the rate of hemorrhage.

The researchers conducted the SWIFT DIRECT trial to investigate this question. They enrolled patients with acute ischemic stroke due to occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery.

The trial was conducted at 48 sites in seven European countries and Canada. The investigators randomly assigned patients to receive IV alteplase (0.9 mg/kg) plus mechanical thrombectomy with the Solitaire device or to receive direct mechanical thrombectomy with the same device. Treatment was open label, but the assessment of endpoints was blinded.

Investigators assigned 423 patients to treatment, and 408 were included in the full analysis set. Of this group, 201 participants received direct mechanical thrombectomy, and 207 received IV thrombolysis plus thrombectomy. There were three crossovers in each treatment arm.

The primary outcome was functional independence, defined as a Modified Rankin Scale (mRS) score of 0-2, at 90 days. Secondary outcomes included mortality at 90 days, mRS shift, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, successful reperfusion, and symptomatic and asymptomatic intracranial hemorrhage (ICH).
 

Noninferiority not demonstrated

At baseline, patient characteristics were well balanced between the treatment groups. The median age of the patients was 72 years, and about 50% of participants were women. The median NIHSS score was 17 in both arms.

Approximately 57% of patients who underwent direct thrombectomy and 65% of those who received IV thrombolysis plus thrombectomy were functionally independent at 90 days, the primary outcome.

In addition, the researchers found no difference in mRS shift, mortality at 90 days, or change in NIHSS score at 24 hours. Postinterventional reperfusion was very high in both arms and was higher in patients who received IV tissue plasminogen activator, compared with those who received direct mechanical thrombectomy, said Dr. Fischer.

The rate of successful postinterventional reperfusion, however, was higher among patients who received thrombolysis than among those who underwent direct thrombectomy. The rate of symptomatic ICH was 1.5% in the direct thrombectomy group and 4.9% in the thrombolysis-plus-thrombectomy group.
 

New endpoints needed?

The investigators used noninferiority margins of 12%. “This question about the noninferiority margins, that’s a very tricky and difficult one in randomized clinical trials,” said Dr. Fischer. The investigators defined their margin using the 2015 HERMES data because no trials had yet compared direct mechanical thrombectomy and bridging thrombolysis at the time.

The researchers are performing a pooled analysis of all the trials that compared bridging thrombolysis with direct mechanical thrombectomy. “We are therefore looking at several margins, and I think this is the way we should look at these noninferiority margins,” said Dr. Fischer. “There’s not a clear-cut level which you can define.”

Enrollment in the trial was well balanced with respect to gender, which is not always the case in stroke studies, said Kevin Sheth, MD, professor of neurology and neurosurgery at Yale School of Medicine, New Haven, Conn., who commented on the study for this news organization.

The findings indicate that the likelihood of there being a difference between groups on this question is low, said Dr. Sheth. Both groups had large-vessel occlusion, both received thrombectomy, and both achieved reperfusion. But the higher rate of successful reperfusion in the bridging cohort was not reflected in any of the clinical endpoints that the investigators examined.

Observing a difference in this context will require very large trials or different endpoints that are more responsive to the intervention, said Dr. Sheth. “This is going to be a challenge for not just this but for any neuroprotection trial in the future,” he said.

The study was supported by Medtronic. Dr. Fischer has served as a consultant for Medtronic, Stryker, and CSL Behring. Dr. Sheth has disclosed no relevant financial relationships.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

Mortality from cancer has dropped substantially in the United States over the past 5 decades, according to a new analysis.

Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.

The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.

“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.

Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.

The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.

The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.

“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.

Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.

In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”

However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.

The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.

“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Mortality from cancer has dropped substantially in the United States over the past 5 decades, according to a new analysis.

Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.

The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.

“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.

Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.

The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.

The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.

“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.

Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.

In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”

However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.

The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.

“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Mortality from cancer has dropped substantially in the United States over the past 5 decades, according to a new analysis.

Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.

The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.

“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.

Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.

The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.

The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.

“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.

Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.

In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”

However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.

The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.

“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Taking a daily multivitamin for 3 years is associated with a 60% slowing of cognitive aging, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.

©Graça Victoria/iStockphoto.com

In addition to testing the effect of a daily multivitamin on cognition, the COSMOS-Mind study examined the effect of cocoa flavanols, but showed no beneficial effect.

The findings “may have important public health implications, particularly for brain health, given the accessibility of multivitamins and minerals, and their low cost and safety,” said study investigator Laura D. Baker, PhD, professor, gerontology and geriatric medicine, Wake Forest University, Winston-Salem, N.C.

The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.

 

Placebo-controlled study

The study is a substudy of a large parent trial that compared the effects of cocoa extract (500 mg/day cocoa flavanols) and a standard multivitamin-mineral (MVM) to placebo on cardiovascular and cancer outcomes in more than 21,000 older participants.

COSMOS-Mind included 2,262 adults aged 65 and over without dementia who underwent cognitive testing at baseline and annually for 3 years. The mean age at baseline was 73 years, and 40.4% were men. Most participants (88.7%) were non-Hispanic White and almost half (49.2%) had some post-college education.

All study groups were balanced with respect to demographics, CVD history, diabetes, depression, smoking status, alcohol intake, chocolate intake, and prior multivitamin use. Baseline cognitive scores were similar between study groups. Researchers had complete data on 77% of study participants.

The primary endpoint was the effect of cocoa extract (CE) vs. placebo on Global Cognitive Function composite score. The secondary outcome was the effect of MVM vs. placebo on global cognitive function.

Additional outcomes included the impact of supplements on executive function and memory and the treatment effects for prespecified subgroups, including subjects with a history of CVD.

Using a graph of change over time, Dr. Baker showed there was no effect of cocoa on global cognitive function (effect: 0.03; 95% confidence interval, –0.02 to 0.08; P = .28). “We see the to-be-expected practice effects, but there’s no separation between the active and placebo groups,” she said.

It was a different story for MVM. Here, there was the same practice effect, but the graph showed the lines separated for global cognitive function composite score (effect: 0.07; 95% CI, 0.02-0.12; P = .007).

“We see a positive effect of multivitamins for the active group relative to placebo, peaking at 2 years and then remaining stable over time,” said Dr. Baker.

There were similar findings with MVM for the memory composite score, and the executive function composite score. “We have significance in all three, where the two lines do separate over and above the practice effects,” said Dr. Baker.
 

New evidence

Investigators found a baseline history of CVD, including transient ischemic attack, heart failure, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and stent, but not myocardial infarction or stroke as these were excluded in the parent trial because they affected the response to multivitamins.

As expected, those with CVD had lower cognitive scores at baseline. “But after an initial bump due to practice effect, at year 1, the cardiovascular disease history folks continue to benefit from multivitamins, whereas those who got placebo multivitamins continue to decline over time,” said Dr. Baker.

Based on information from a baseline scatter plot of cognitive function scores by age, the study’s modeling estimated the multivitamin treatment effect had a positive benefit of .028 standard deviations (SD) per year.

“Daily multivitamin-mineral supplementation appears to slow cognitive aging by 60% or by 1.8 years,” Dr. Baker added.

To date, the effect of MVM supplementation on cognition has been tested in only one large randomized clinical trial – the Physicians Health Study II. That study did not show an effect, but included only older male physicians – and cognitive testing began 2.5 years after randomization, said Dr. Baker.

“Our study provides new evidence that daily multivitamin supplementation may benefit cognitive function in older women and men, and the multivitamin effects may be more pronounced in participants with cardiovascular disease,” she noted.

For effects of multivitamins on Alzheimer’s disease prevalence and progression, “stay tuned,” Dr. Baker concluded.

Following the presentation, session cochair Suzanne Schindler, MD, PhD, instructor in the department of neurology at Washington University, St. Louis, said she and her colleagues “always check vitamin B₁₂ levels” in patients with memory and cognitive difficulties and wondered if study subjects with a low level or deficiency of vitamin B₁₂ benefited from the intervention.

“We are asking ourselves that as well,” said Dr. Baker.

“Some of this is a work in progress,” Dr. Baker added. “We still need to look at that more in-depth to understand whether it might be a mechanism for improvement. I think the results are still out on that topic.”

The study received support from the National Institute on Aging. Pfizer Consumer Healthcare (now GSK Consumer Healthcare) provided study pills and packaging. Dr. Baker has disclosed no relevant financial relationships.
 

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

Taking a daily multivitamin for 3 years is associated with a 60% slowing of cognitive aging, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.

©Graça Victoria/iStockphoto.com

In addition to testing the effect of a daily multivitamin on cognition, the COSMOS-Mind study examined the effect of cocoa flavanols, but showed no beneficial effect.

The findings “may have important public health implications, particularly for brain health, given the accessibility of multivitamins and minerals, and their low cost and safety,” said study investigator Laura D. Baker, PhD, professor, gerontology and geriatric medicine, Wake Forest University, Winston-Salem, N.C.

The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.

 

Placebo-controlled study

The study is a substudy of a large parent trial that compared the effects of cocoa extract (500 mg/day cocoa flavanols) and a standard multivitamin-mineral (MVM) to placebo on cardiovascular and cancer outcomes in more than 21,000 older participants.

COSMOS-Mind included 2,262 adults aged 65 and over without dementia who underwent cognitive testing at baseline and annually for 3 years. The mean age at baseline was 73 years, and 40.4% were men. Most participants (88.7%) were non-Hispanic White and almost half (49.2%) had some post-college education.

All study groups were balanced with respect to demographics, CVD history, diabetes, depression, smoking status, alcohol intake, chocolate intake, and prior multivitamin use. Baseline cognitive scores were similar between study groups. Researchers had complete data on 77% of study participants.

The primary endpoint was the effect of cocoa extract (CE) vs. placebo on Global Cognitive Function composite score. The secondary outcome was the effect of MVM vs. placebo on global cognitive function.

Additional outcomes included the impact of supplements on executive function and memory and the treatment effects for prespecified subgroups, including subjects with a history of CVD.

Using a graph of change over time, Dr. Baker showed there was no effect of cocoa on global cognitive function (effect: 0.03; 95% confidence interval, –0.02 to 0.08; P = .28). “We see the to-be-expected practice effects, but there’s no separation between the active and placebo groups,” she said.

It was a different story for MVM. Here, there was the same practice effect, but the graph showed the lines separated for global cognitive function composite score (effect: 0.07; 95% CI, 0.02-0.12; P = .007).

“We see a positive effect of multivitamins for the active group relative to placebo, peaking at 2 years and then remaining stable over time,” said Dr. Baker.

There were similar findings with MVM for the memory composite score, and the executive function composite score. “We have significance in all three, where the two lines do separate over and above the practice effects,” said Dr. Baker.
 

New evidence

Investigators found a baseline history of CVD, including transient ischemic attack, heart failure, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and stent, but not myocardial infarction or stroke as these were excluded in the parent trial because they affected the response to multivitamins.

As expected, those with CVD had lower cognitive scores at baseline. “But after an initial bump due to practice effect, at year 1, the cardiovascular disease history folks continue to benefit from multivitamins, whereas those who got placebo multivitamins continue to decline over time,” said Dr. Baker.

Based on information from a baseline scatter plot of cognitive function scores by age, the study’s modeling estimated the multivitamin treatment effect had a positive benefit of .028 standard deviations (SD) per year.

“Daily multivitamin-mineral supplementation appears to slow cognitive aging by 60% or by 1.8 years,” Dr. Baker added.

To date, the effect of MVM supplementation on cognition has been tested in only one large randomized clinical trial – the Physicians Health Study II. That study did not show an effect, but included only older male physicians – and cognitive testing began 2.5 years after randomization, said Dr. Baker.

“Our study provides new evidence that daily multivitamin supplementation may benefit cognitive function in older women and men, and the multivitamin effects may be more pronounced in participants with cardiovascular disease,” she noted.

For effects of multivitamins on Alzheimer’s disease prevalence and progression, “stay tuned,” Dr. Baker concluded.

Following the presentation, session cochair Suzanne Schindler, MD, PhD, instructor in the department of neurology at Washington University, St. Louis, said she and her colleagues “always check vitamin B₁₂ levels” in patients with memory and cognitive difficulties and wondered if study subjects with a low level or deficiency of vitamin B₁₂ benefited from the intervention.

“We are asking ourselves that as well,” said Dr. Baker.

“Some of this is a work in progress,” Dr. Baker added. “We still need to look at that more in-depth to understand whether it might be a mechanism for improvement. I think the results are still out on that topic.”

The study received support from the National Institute on Aging. Pfizer Consumer Healthcare (now GSK Consumer Healthcare) provided study pills and packaging. Dr. Baker has disclosed no relevant financial relationships.
 

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

Taking a daily multivitamin for 3 years is associated with a 60% slowing of cognitive aging, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.

©Graça Victoria/iStockphoto.com

In addition to testing the effect of a daily multivitamin on cognition, the COSMOS-Mind study examined the effect of cocoa flavanols, but showed no beneficial effect.

The findings “may have important public health implications, particularly for brain health, given the accessibility of multivitamins and minerals, and their low cost and safety,” said study investigator Laura D. Baker, PhD, professor, gerontology and geriatric medicine, Wake Forest University, Winston-Salem, N.C.

The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.

 

Placebo-controlled study

The study is a substudy of a large parent trial that compared the effects of cocoa extract (500 mg/day cocoa flavanols) and a standard multivitamin-mineral (MVM) to placebo on cardiovascular and cancer outcomes in more than 21,000 older participants.

COSMOS-Mind included 2,262 adults aged 65 and over without dementia who underwent cognitive testing at baseline and annually for 3 years. The mean age at baseline was 73 years, and 40.4% were men. Most participants (88.7%) were non-Hispanic White and almost half (49.2%) had some post-college education.

All study groups were balanced with respect to demographics, CVD history, diabetes, depression, smoking status, alcohol intake, chocolate intake, and prior multivitamin use. Baseline cognitive scores were similar between study groups. Researchers had complete data on 77% of study participants.

The primary endpoint was the effect of cocoa extract (CE) vs. placebo on Global Cognitive Function composite score. The secondary outcome was the effect of MVM vs. placebo on global cognitive function.

Additional outcomes included the impact of supplements on executive function and memory and the treatment effects for prespecified subgroups, including subjects with a history of CVD.

Using a graph of change over time, Dr. Baker showed there was no effect of cocoa on global cognitive function (effect: 0.03; 95% confidence interval, –0.02 to 0.08; P = .28). “We see the to-be-expected practice effects, but there’s no separation between the active and placebo groups,” she said.

It was a different story for MVM. Here, there was the same practice effect, but the graph showed the lines separated for global cognitive function composite score (effect: 0.07; 95% CI, 0.02-0.12; P = .007).

“We see a positive effect of multivitamins for the active group relative to placebo, peaking at 2 years and then remaining stable over time,” said Dr. Baker.

There were similar findings with MVM for the memory composite score, and the executive function composite score. “We have significance in all three, where the two lines do separate over and above the practice effects,” said Dr. Baker.
 

New evidence

Investigators found a baseline history of CVD, including transient ischemic attack, heart failure, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and stent, but not myocardial infarction or stroke as these were excluded in the parent trial because they affected the response to multivitamins.

As expected, those with CVD had lower cognitive scores at baseline. “But after an initial bump due to practice effect, at year 1, the cardiovascular disease history folks continue to benefit from multivitamins, whereas those who got placebo multivitamins continue to decline over time,” said Dr. Baker.

Based on information from a baseline scatter plot of cognitive function scores by age, the study’s modeling estimated the multivitamin treatment effect had a positive benefit of .028 standard deviations (SD) per year.

“Daily multivitamin-mineral supplementation appears to slow cognitive aging by 60% or by 1.8 years,” Dr. Baker added.

To date, the effect of MVM supplementation on cognition has been tested in only one large randomized clinical trial – the Physicians Health Study II. That study did not show an effect, but included only older male physicians – and cognitive testing began 2.5 years after randomization, said Dr. Baker.

“Our study provides new evidence that daily multivitamin supplementation may benefit cognitive function in older women and men, and the multivitamin effects may be more pronounced in participants with cardiovascular disease,” she noted.

For effects of multivitamins on Alzheimer’s disease prevalence and progression, “stay tuned,” Dr. Baker concluded.

Following the presentation, session cochair Suzanne Schindler, MD, PhD, instructor in the department of neurology at Washington University, St. Louis, said she and her colleagues “always check vitamin B₁₂ levels” in patients with memory and cognitive difficulties and wondered if study subjects with a low level or deficiency of vitamin B₁₂ benefited from the intervention.

“We are asking ourselves that as well,” said Dr. Baker.

“Some of this is a work in progress,” Dr. Baker added. “We still need to look at that more in-depth to understand whether it might be a mechanism for improvement. I think the results are still out on that topic.”

The study received support from the National Institute on Aging. Pfizer Consumer Healthcare (now GSK Consumer Healthcare) provided study pills and packaging. Dr. Baker has disclosed no relevant financial relationships.
 

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

Up to one-third of patients with multiple sclerosis (MS) treated with the B-cell depleting monoclonal antibody ocrelizumab (Ocrevus) show some degree of repletion of B-cells toward the end of the 6-month infusion cycle. However, there are no corresponding worsening of symptoms or signs of a “wearing off” effect, new research shows.

“Most people expect that since this is a B-cell depleting drug, that if you are not depleting B cells, then that should be reflected clinically and there should be some breakthrough activity,” said study investigator Joshua D. Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care in Wellesley, Massachusetts.

Real-world study

Preapproval clinical trials of ocrelizumab suggest about 5% of patients experience a repletion of B cells. However, the timing and association with breakthrough symptoms were unclear.

To investigate, Dr. Katz and colleagues conducted two studies. The first is a substudy of the prospective ACAPELLA trial to assess ocrelizumab-associated adverse events in a real-world population. The study included 294 patients with relapsing and progressive forms of MS treated with at least two cycles of ocrelizumab, given as infusion once every 6 months.

The results showed that overall, 91 (31%) of the 294 patients had some degree of repletion at one or more timepoints.

In categorizing patients according to their highest CD19 measure after two cycles, 108 patients (64.7%) had no significant repletion of B-cells after infusion, defined as an increase of less than 10 cells/μL, while 45 (26.9%) were considered mild repleters, defined as having increases of 10-49 cells/μL.

Seven patients (4.2%) were moderate repleters, with an increase of 50-79 cells/μL, and 7 (4.2%) were categorized as marked repleters, with increases of 80 or more cells/μL.

Eight patients in the study fully repleted, with values from 114-319 cells/μL, occurring between 23 and 34 weeks of the last infusion.

However, there was no relationship between repletion of the B-cells and clinical or MRI evidence of relapse.

Of note, the proportion of patients who did not have B-cell repletion increased with greater numbers of infusions. Whereas 64.7% were non-repleters at cycle 2, that number increased to 88.8% by cycle 6, with a slight drop to 85.6% being non-repleters by cycle 7 (36 months).

“Mild B-cell repletion was fairly common after two cycles of ocrelizumab, but with repeated dosing, a greater proportion of patients were non-repleters, suggesting that cumulative exposure to ocrelizumab results in greater depletion,” the researchers noted.

However, “while the number of moderate or marked repleters in our study was small, they had a tendency to remain repleters over time with subsequent infusions,” they added.

In looking at patient characteristics, moderate and marketed repleters had higher mean BMI (34.1 and 32.6, respectively) compared with the non- and mild repleters (27.0 and 29.4, respectively; P < .0001).

Dr. Katz noted that the increased risk of B-cell repletion with higher BMI was not a surprise. This association, he said, “makes sense” because patients’ relative exposure to ocrelizumab decreases with higher BMI. Similar patterns with BMI were observed in the clinical trial for ocrelizumab approval, in which patients with lower BMI tended to have greater improvement.
 

No symptom worsening

In the second study, the investigators further examined changes in symptom burden related to the amount of time from ocrelizumab infusion. They evaluated 110 patients, aged 18-80 (mean age 44.8) who had Expanded Disability Status Scale (EDSS) scores between 0-7. Study participants were either initiating ocrelizumab or had been on the drug for at least 1 year.

Symptom burden was evaluated with the Neurological Disorders (Neuro-Qol) questionnaire and SymptoMScreen patient-reported outcomes at the beginning of the study at week 4, and near the end of the ocrelizumab infusion cycle, at week 22.

The researchers found that among 69 participants who completed the questionnaires, there were no significant differences at week 22 versus week 4 across a wide range of symptoms, including walking, spasticity, pain, fatigue, cognitive function, dizziness, and depression between the two timepoints.

The only change on the Neuro-QoL score was in the sleep disturbance domain, which improved marginally at the end of the cycle (P = .052). This study did not evaluate changes in B-cells.

Dr. Katz noted that the inclusion of patients over age of 55 in the study offered important insights.

“Our hypothesis was that we were going to start seeing a higher rate of complications, especially infections, in people who are older and may be at a higher risk of infection and disability,” Dr. Katz noted. “But so far, we haven’t seen any higher risk in older patients or those with more disability than anyone else, which is good news.”
 

Amplification of baseline symptoms not uncommon

Commenting on the research, Scott D. Newsome, DO, current president of the CMSC, noted that although no association was observed between the B-cell repletion and symptoms, amplification of flare-up symptoms that are linked to B-cell depleting therapy infusion timing are not uncommon.

“The ‘wearing-off’ phenomenon is not unique to the B-cell therapies,” said Dr. Newsome, who is also director of Johns Hopkins University’s Neurosciences Consultation and Infusion Center and an associate professor of neurology at the JHU med school. “With natalizumab (Tysabri), patients can have an amplification of baseline symptoms as they come closer to their next infusion, and it has been speculated that maybe it was something biologically happening, such as inflammatory cytokines ramping back up or some other mechanisms.”

“Now that we have the B-cell depleting therapies, we tend see the same kind of pattern, where a few weeks leading up to the next infusion, people will develop these amplified symptoms,” he said.

The possibility of a cumulative effect, appearing to address the B-cell repletion associated with early infusions, could have implications over time, Dr. Newsome noted.

“This is important because if people are going on these therapies long-term, the question we may need to ask is whether they actually need to continue to get an infusion every 6 months,” he said.

As these questions around the safety of long-term immunosuppressant drug use continue, different dosing regimens may need to be considered in order to mitigate potential infection risk, he added.

Dr. Katz reports consulting and/or speakers’ bureau relationships with Alexion, Biogen, EMD Serono, Genentech, Novartis, and Sanofi. Dr. Newsome reports relationships with Autobahn, BioIncept, Biogen, Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, and MedDay Pharmaceuticals.

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

Up to one-third of patients with multiple sclerosis (MS) treated with the B-cell depleting monoclonal antibody ocrelizumab (Ocrevus) show some degree of repletion of B-cells toward the end of the 6-month infusion cycle. However, there are no corresponding worsening of symptoms or signs of a “wearing off” effect, new research shows.

“Most people expect that since this is a B-cell depleting drug, that if you are not depleting B cells, then that should be reflected clinically and there should be some breakthrough activity,” said study investigator Joshua D. Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care in Wellesley, Massachusetts.

Real-world study

Preapproval clinical trials of ocrelizumab suggest about 5% of patients experience a repletion of B cells. However, the timing and association with breakthrough symptoms were unclear.

To investigate, Dr. Katz and colleagues conducted two studies. The first is a substudy of the prospective ACAPELLA trial to assess ocrelizumab-associated adverse events in a real-world population. The study included 294 patients with relapsing and progressive forms of MS treated with at least two cycles of ocrelizumab, given as infusion once every 6 months.

The results showed that overall, 91 (31%) of the 294 patients had some degree of repletion at one or more timepoints.

In categorizing patients according to their highest CD19 measure after two cycles, 108 patients (64.7%) had no significant repletion of B-cells after infusion, defined as an increase of less than 10 cells/μL, while 45 (26.9%) were considered mild repleters, defined as having increases of 10-49 cells/μL.

Seven patients (4.2%) were moderate repleters, with an increase of 50-79 cells/μL, and 7 (4.2%) were categorized as marked repleters, with increases of 80 or more cells/μL.

Eight patients in the study fully repleted, with values from 114-319 cells/μL, occurring between 23 and 34 weeks of the last infusion.

However, there was no relationship between repletion of the B-cells and clinical or MRI evidence of relapse.

Of note, the proportion of patients who did not have B-cell repletion increased with greater numbers of infusions. Whereas 64.7% were non-repleters at cycle 2, that number increased to 88.8% by cycle 6, with a slight drop to 85.6% being non-repleters by cycle 7 (36 months).

“Mild B-cell repletion was fairly common after two cycles of ocrelizumab, but with repeated dosing, a greater proportion of patients were non-repleters, suggesting that cumulative exposure to ocrelizumab results in greater depletion,” the researchers noted.

However, “while the number of moderate or marked repleters in our study was small, they had a tendency to remain repleters over time with subsequent infusions,” they added.

In looking at patient characteristics, moderate and marketed repleters had higher mean BMI (34.1 and 32.6, respectively) compared with the non- and mild repleters (27.0 and 29.4, respectively; P < .0001).

Dr. Katz noted that the increased risk of B-cell repletion with higher BMI was not a surprise. This association, he said, “makes sense” because patients’ relative exposure to ocrelizumab decreases with higher BMI. Similar patterns with BMI were observed in the clinical trial for ocrelizumab approval, in which patients with lower BMI tended to have greater improvement.
 

No symptom worsening

In the second study, the investigators further examined changes in symptom burden related to the amount of time from ocrelizumab infusion. They evaluated 110 patients, aged 18-80 (mean age 44.8) who had Expanded Disability Status Scale (EDSS) scores between 0-7. Study participants were either initiating ocrelizumab or had been on the drug for at least 1 year.

Symptom burden was evaluated with the Neurological Disorders (Neuro-Qol) questionnaire and SymptoMScreen patient-reported outcomes at the beginning of the study at week 4, and near the end of the ocrelizumab infusion cycle, at week 22.

The researchers found that among 69 participants who completed the questionnaires, there were no significant differences at week 22 versus week 4 across a wide range of symptoms, including walking, spasticity, pain, fatigue, cognitive function, dizziness, and depression between the two timepoints.

The only change on the Neuro-QoL score was in the sleep disturbance domain, which improved marginally at the end of the cycle (P = .052). This study did not evaluate changes in B-cells.

Dr. Katz noted that the inclusion of patients over age of 55 in the study offered important insights.

“Our hypothesis was that we were going to start seeing a higher rate of complications, especially infections, in people who are older and may be at a higher risk of infection and disability,” Dr. Katz noted. “But so far, we haven’t seen any higher risk in older patients or those with more disability than anyone else, which is good news.”
 

Amplification of baseline symptoms not uncommon

Commenting on the research, Scott D. Newsome, DO, current president of the CMSC, noted that although no association was observed between the B-cell repletion and symptoms, amplification of flare-up symptoms that are linked to B-cell depleting therapy infusion timing are not uncommon.

“The ‘wearing-off’ phenomenon is not unique to the B-cell therapies,” said Dr. Newsome, who is also director of Johns Hopkins University’s Neurosciences Consultation and Infusion Center and an associate professor of neurology at the JHU med school. “With natalizumab (Tysabri), patients can have an amplification of baseline symptoms as they come closer to their next infusion, and it has been speculated that maybe it was something biologically happening, such as inflammatory cytokines ramping back up or some other mechanisms.”

“Now that we have the B-cell depleting therapies, we tend see the same kind of pattern, where a few weeks leading up to the next infusion, people will develop these amplified symptoms,” he said.

The possibility of a cumulative effect, appearing to address the B-cell repletion associated with early infusions, could have implications over time, Dr. Newsome noted.

“This is important because if people are going on these therapies long-term, the question we may need to ask is whether they actually need to continue to get an infusion every 6 months,” he said.

As these questions around the safety of long-term immunosuppressant drug use continue, different dosing regimens may need to be considered in order to mitigate potential infection risk, he added.

Dr. Katz reports consulting and/or speakers’ bureau relationships with Alexion, Biogen, EMD Serono, Genentech, Novartis, and Sanofi. Dr. Newsome reports relationships with Autobahn, BioIncept, Biogen, Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, and MedDay Pharmaceuticals.

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

Up to one-third of patients with multiple sclerosis (MS) treated with the B-cell depleting monoclonal antibody ocrelizumab (Ocrevus) show some degree of repletion of B-cells toward the end of the 6-month infusion cycle. However, there are no corresponding worsening of symptoms or signs of a “wearing off” effect, new research shows.

“Most people expect that since this is a B-cell depleting drug, that if you are not depleting B cells, then that should be reflected clinically and there should be some breakthrough activity,” said study investigator Joshua D. Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care in Wellesley, Massachusetts.

Real-world study

Preapproval clinical trials of ocrelizumab suggest about 5% of patients experience a repletion of B cells. However, the timing and association with breakthrough symptoms were unclear.

To investigate, Dr. Katz and colleagues conducted two studies. The first is a substudy of the prospective ACAPELLA trial to assess ocrelizumab-associated adverse events in a real-world population. The study included 294 patients with relapsing and progressive forms of MS treated with at least two cycles of ocrelizumab, given as infusion once every 6 months.

The results showed that overall, 91 (31%) of the 294 patients had some degree of repletion at one or more timepoints.

In categorizing patients according to their highest CD19 measure after two cycles, 108 patients (64.7%) had no significant repletion of B-cells after infusion, defined as an increase of less than 10 cells/μL, while 45 (26.9%) were considered mild repleters, defined as having increases of 10-49 cells/μL.

Seven patients (4.2%) were moderate repleters, with an increase of 50-79 cells/μL, and 7 (4.2%) were categorized as marked repleters, with increases of 80 or more cells/μL.

Eight patients in the study fully repleted, with values from 114-319 cells/μL, occurring between 23 and 34 weeks of the last infusion.

However, there was no relationship between repletion of the B-cells and clinical or MRI evidence of relapse.

Of note, the proportion of patients who did not have B-cell repletion increased with greater numbers of infusions. Whereas 64.7% were non-repleters at cycle 2, that number increased to 88.8% by cycle 6, with a slight drop to 85.6% being non-repleters by cycle 7 (36 months).

“Mild B-cell repletion was fairly common after two cycles of ocrelizumab, but with repeated dosing, a greater proportion of patients were non-repleters, suggesting that cumulative exposure to ocrelizumab results in greater depletion,” the researchers noted.

However, “while the number of moderate or marked repleters in our study was small, they had a tendency to remain repleters over time with subsequent infusions,” they added.

In looking at patient characteristics, moderate and marketed repleters had higher mean BMI (34.1 and 32.6, respectively) compared with the non- and mild repleters (27.0 and 29.4, respectively; P < .0001).

Dr. Katz noted that the increased risk of B-cell repletion with higher BMI was not a surprise. This association, he said, “makes sense” because patients’ relative exposure to ocrelizumab decreases with higher BMI. Similar patterns with BMI were observed in the clinical trial for ocrelizumab approval, in which patients with lower BMI tended to have greater improvement.
 

No symptom worsening

In the second study, the investigators further examined changes in symptom burden related to the amount of time from ocrelizumab infusion. They evaluated 110 patients, aged 18-80 (mean age 44.8) who had Expanded Disability Status Scale (EDSS) scores between 0-7. Study participants were either initiating ocrelizumab or had been on the drug for at least 1 year.

Symptom burden was evaluated with the Neurological Disorders (Neuro-Qol) questionnaire and SymptoMScreen patient-reported outcomes at the beginning of the study at week 4, and near the end of the ocrelizumab infusion cycle, at week 22.

The researchers found that among 69 participants who completed the questionnaires, there were no significant differences at week 22 versus week 4 across a wide range of symptoms, including walking, spasticity, pain, fatigue, cognitive function, dizziness, and depression between the two timepoints.

The only change on the Neuro-QoL score was in the sleep disturbance domain, which improved marginally at the end of the cycle (P = .052). This study did not evaluate changes in B-cells.

Dr. Katz noted that the inclusion of patients over age of 55 in the study offered important insights.

“Our hypothesis was that we were going to start seeing a higher rate of complications, especially infections, in people who are older and may be at a higher risk of infection and disability,” Dr. Katz noted. “But so far, we haven’t seen any higher risk in older patients or those with more disability than anyone else, which is good news.”
 

Amplification of baseline symptoms not uncommon

Commenting on the research, Scott D. Newsome, DO, current president of the CMSC, noted that although no association was observed between the B-cell repletion and symptoms, amplification of flare-up symptoms that are linked to B-cell depleting therapy infusion timing are not uncommon.

“The ‘wearing-off’ phenomenon is not unique to the B-cell therapies,” said Dr. Newsome, who is also director of Johns Hopkins University’s Neurosciences Consultation and Infusion Center and an associate professor of neurology at the JHU med school. “With natalizumab (Tysabri), patients can have an amplification of baseline symptoms as they come closer to their next infusion, and it has been speculated that maybe it was something biologically happening, such as inflammatory cytokines ramping back up or some other mechanisms.”

“Now that we have the B-cell depleting therapies, we tend see the same kind of pattern, where a few weeks leading up to the next infusion, people will develop these amplified symptoms,” he said.

The possibility of a cumulative effect, appearing to address the B-cell repletion associated with early infusions, could have implications over time, Dr. Newsome noted.

“This is important because if people are going on these therapies long-term, the question we may need to ask is whether they actually need to continue to get an infusion every 6 months,” he said.

As these questions around the safety of long-term immunosuppressant drug use continue, different dosing regimens may need to be considered in order to mitigate potential infection risk, he added.

Dr. Katz reports consulting and/or speakers’ bureau relationships with Alexion, Biogen, EMD Serono, Genentech, Novartis, and Sanofi. Dr. Newsome reports relationships with Autobahn, BioIncept, Biogen, Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, and MedDay Pharmaceuticals.

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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