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California wildfires caused uptick in clinic visits for atopic dermatitis, itch
During the deadliest wildfire in California’s history in 2018, dermatology clinics 175 miles away at the University of California, San Francisco, experienced an increase in the number of pediatric and adult visits for pruritus and atopic dermatitis associated with air pollution created from the wildfire, according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
Raj Fadadu, a medical student at the University of California, San Francisco, said in his presentation.
Not many studies have examined this potential association, but includes those that have found significant positive associations between exposure to air pollution and pruritus, the development of AD, and exacerbation of AD (J Allergy Clin Immunol. 2014 Nov;134[5]:993-9). Another study found outpatient visits for patients with eczema and dermatitis in Beijing increased as the level of particulate matter, nitrogen dioxide, and sulfur dioxide concentrations increased (Environ Sci Process Impacts. 2019 Jan 23;21[1]:163-73).
Mr. Faduda and colleagues set out to determine whether the number of appointments for and severity of skin disease increased as a result of the 2018 Camp Fire, which started in Paradise, Calif., using measures of air pollution and clinic visits in years where California did not experience a wildfire event as controls. Using the National Oceanic and Atmospheric Administration Hazard Mapping System for fire and smoke, the researchers graphed smoke plume density scores and particulate matter (PM2.5) concentrations in the area. They then calculated the number of UCSF dermatology clinic visits for AD/eczema, and measured severity of skin disease with appointments for itch symptoms, and the number of prescribed medications during that time using ICD-10 codes.
The Camp Fire rapidly spread over a period of 17 days, between Nov. 8 and 25, 2018, during which time, PM2.5 particulate matter concentrations increased 10-fold, while the NOAA smoke plume density score sharply increased. More pediatric and adult patients also seemed to be visiting clinics during this time, compared with several weeks before and several weeks after the fire, prompting a more expanded analysis of this signal, Mr. Fadadu said.
He and his coinvestigators compared data between October 2015 and February 2016 – a period of time where there were no wildfires in California – with data in 2018, when the Camp Fire occurred. They collected data on 3,448 adults and 699 children across 3 years with a total of 5,539 adult appointments for AD, 924 pediatric appointments for AD, 1,319 adult itch appointments, and 294 pediatric itch appointments. Cumulative and exposure lags were used to measure the effect of the wildfire in a Poisson regression analysis.
They found that, during the wildfire, pediatric AD weekly clinic visits were 1.75 times higher (95% confidence interval, 1.21-2.50) and pediatric itch visits were 2.10 times higher (95% CI, 1.44-3.00), compared with weeks where there was no fire. During the wildfire, pediatric AD clinic visits increased by 8% (rate ratio, 1.08; 95% CI, 1.04-1.12) per 10 mcg/m3 increase in PM2.5 concentration.
In adults, clinic visits for AD were 1.28 times higher (95% CI, 1.08-1.51) during the wildfire, compared with nonfire weeks. While there was a positive association between pollution exposure and adult AD, “this effect is less than what we observed” for pediatric AD visits, said Mr. Fadadu. Air pollution was positively associated with the development of itch symptoms in adults and more prescriptions for AD medications, but the results were not statistically significant.
“This may be explained by the fact that 80% of pediatric itch patients carried an AD diagnosis, while in contrast, only half of the adult itch patients also have a diagnosis of AD,” he said.
While there are several possible limitations of the research, including assessment of air pollution exposure, Mr. Fadadu said, “these results can inform how dermatologists counsel patients during future episodes of poor air quality, as well as expand comprehension of the broader health effects of climate change that can significantly impact quality of life.”
This study was funded by the UCSF Summer Explore Fellowship, Marguerite Schoeneman Award, and Joint Medical Program Thesis Grant.
During the deadliest wildfire in California’s history in 2018, dermatology clinics 175 miles away at the University of California, San Francisco, experienced an increase in the number of pediatric and adult visits for pruritus and atopic dermatitis associated with air pollution created from the wildfire, according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
Raj Fadadu, a medical student at the University of California, San Francisco, said in his presentation.
Not many studies have examined this potential association, but includes those that have found significant positive associations between exposure to air pollution and pruritus, the development of AD, and exacerbation of AD (J Allergy Clin Immunol. 2014 Nov;134[5]:993-9). Another study found outpatient visits for patients with eczema and dermatitis in Beijing increased as the level of particulate matter, nitrogen dioxide, and sulfur dioxide concentrations increased (Environ Sci Process Impacts. 2019 Jan 23;21[1]:163-73).
Mr. Faduda and colleagues set out to determine whether the number of appointments for and severity of skin disease increased as a result of the 2018 Camp Fire, which started in Paradise, Calif., using measures of air pollution and clinic visits in years where California did not experience a wildfire event as controls. Using the National Oceanic and Atmospheric Administration Hazard Mapping System for fire and smoke, the researchers graphed smoke plume density scores and particulate matter (PM2.5) concentrations in the area. They then calculated the number of UCSF dermatology clinic visits for AD/eczema, and measured severity of skin disease with appointments for itch symptoms, and the number of prescribed medications during that time using ICD-10 codes.
The Camp Fire rapidly spread over a period of 17 days, between Nov. 8 and 25, 2018, during which time, PM2.5 particulate matter concentrations increased 10-fold, while the NOAA smoke plume density score sharply increased. More pediatric and adult patients also seemed to be visiting clinics during this time, compared with several weeks before and several weeks after the fire, prompting a more expanded analysis of this signal, Mr. Fadadu said.
He and his coinvestigators compared data between October 2015 and February 2016 – a period of time where there were no wildfires in California – with data in 2018, when the Camp Fire occurred. They collected data on 3,448 adults and 699 children across 3 years with a total of 5,539 adult appointments for AD, 924 pediatric appointments for AD, 1,319 adult itch appointments, and 294 pediatric itch appointments. Cumulative and exposure lags were used to measure the effect of the wildfire in a Poisson regression analysis.
They found that, during the wildfire, pediatric AD weekly clinic visits were 1.75 times higher (95% confidence interval, 1.21-2.50) and pediatric itch visits were 2.10 times higher (95% CI, 1.44-3.00), compared with weeks where there was no fire. During the wildfire, pediatric AD clinic visits increased by 8% (rate ratio, 1.08; 95% CI, 1.04-1.12) per 10 mcg/m3 increase in PM2.5 concentration.
In adults, clinic visits for AD were 1.28 times higher (95% CI, 1.08-1.51) during the wildfire, compared with nonfire weeks. While there was a positive association between pollution exposure and adult AD, “this effect is less than what we observed” for pediatric AD visits, said Mr. Fadadu. Air pollution was positively associated with the development of itch symptoms in adults and more prescriptions for AD medications, but the results were not statistically significant.
“This may be explained by the fact that 80% of pediatric itch patients carried an AD diagnosis, while in contrast, only half of the adult itch patients also have a diagnosis of AD,” he said.
While there are several possible limitations of the research, including assessment of air pollution exposure, Mr. Fadadu said, “these results can inform how dermatologists counsel patients during future episodes of poor air quality, as well as expand comprehension of the broader health effects of climate change that can significantly impact quality of life.”
This study was funded by the UCSF Summer Explore Fellowship, Marguerite Schoeneman Award, and Joint Medical Program Thesis Grant.
During the deadliest wildfire in California’s history in 2018, dermatology clinics 175 miles away at the University of California, San Francisco, experienced an increase in the number of pediatric and adult visits for pruritus and atopic dermatitis associated with air pollution created from the wildfire, according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
Raj Fadadu, a medical student at the University of California, San Francisco, said in his presentation.
Not many studies have examined this potential association, but includes those that have found significant positive associations between exposure to air pollution and pruritus, the development of AD, and exacerbation of AD (J Allergy Clin Immunol. 2014 Nov;134[5]:993-9). Another study found outpatient visits for patients with eczema and dermatitis in Beijing increased as the level of particulate matter, nitrogen dioxide, and sulfur dioxide concentrations increased (Environ Sci Process Impacts. 2019 Jan 23;21[1]:163-73).
Mr. Faduda and colleagues set out to determine whether the number of appointments for and severity of skin disease increased as a result of the 2018 Camp Fire, which started in Paradise, Calif., using measures of air pollution and clinic visits in years where California did not experience a wildfire event as controls. Using the National Oceanic and Atmospheric Administration Hazard Mapping System for fire and smoke, the researchers graphed smoke plume density scores and particulate matter (PM2.5) concentrations in the area. They then calculated the number of UCSF dermatology clinic visits for AD/eczema, and measured severity of skin disease with appointments for itch symptoms, and the number of prescribed medications during that time using ICD-10 codes.
The Camp Fire rapidly spread over a period of 17 days, between Nov. 8 and 25, 2018, during which time, PM2.5 particulate matter concentrations increased 10-fold, while the NOAA smoke plume density score sharply increased. More pediatric and adult patients also seemed to be visiting clinics during this time, compared with several weeks before and several weeks after the fire, prompting a more expanded analysis of this signal, Mr. Fadadu said.
He and his coinvestigators compared data between October 2015 and February 2016 – a period of time where there were no wildfires in California – with data in 2018, when the Camp Fire occurred. They collected data on 3,448 adults and 699 children across 3 years with a total of 5,539 adult appointments for AD, 924 pediatric appointments for AD, 1,319 adult itch appointments, and 294 pediatric itch appointments. Cumulative and exposure lags were used to measure the effect of the wildfire in a Poisson regression analysis.
They found that, during the wildfire, pediatric AD weekly clinic visits were 1.75 times higher (95% confidence interval, 1.21-2.50) and pediatric itch visits were 2.10 times higher (95% CI, 1.44-3.00), compared with weeks where there was no fire. During the wildfire, pediatric AD clinic visits increased by 8% (rate ratio, 1.08; 95% CI, 1.04-1.12) per 10 mcg/m3 increase in PM2.5 concentration.
In adults, clinic visits for AD were 1.28 times higher (95% CI, 1.08-1.51) during the wildfire, compared with nonfire weeks. While there was a positive association between pollution exposure and adult AD, “this effect is less than what we observed” for pediatric AD visits, said Mr. Fadadu. Air pollution was positively associated with the development of itch symptoms in adults and more prescriptions for AD medications, but the results were not statistically significant.
“This may be explained by the fact that 80% of pediatric itch patients carried an AD diagnosis, while in contrast, only half of the adult itch patients also have a diagnosis of AD,” he said.
While there are several possible limitations of the research, including assessment of air pollution exposure, Mr. Fadadu said, “these results can inform how dermatologists counsel patients during future episodes of poor air quality, as well as expand comprehension of the broader health effects of climate change that can significantly impact quality of life.”
This study was funded by the UCSF Summer Explore Fellowship, Marguerite Schoeneman Award, and Joint Medical Program Thesis Grant.
FROM SID 2020
Nonpharmacologic ankylosing spondylitis recommendations not followed
Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.
However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.
To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.
Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.
Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.
In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.
It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.
Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.
A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*
Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.
It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.
The study’s funding source and disclosures – if any – weren’t reported.
*Correction, 6/3/2020: A previous version of this story misattributed this quote.
SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.
Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.
However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.
To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.
Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.
Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.
In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.
It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.
Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.
A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*
Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.
It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.
The study’s funding source and disclosures – if any – weren’t reported.
*Correction, 6/3/2020: A previous version of this story misattributed this quote.
SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.
Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.
However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.
To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.
Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.
Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.
In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.
It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.
Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.
A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*
Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.
It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.
The study’s funding source and disclosures – if any – weren’t reported.
*Correction, 6/3/2020: A previous version of this story misattributed this quote.
SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.
FROM SPARTAN 2020
Standardized protocol guides therapies to reduce VTE after arthroplasty
A simple tool to guide choice of antithrombotic therapy following total joint arthroplasty led to a reduction in pulmonary embolism (PE) after being introduced systemwide, according to a prospectively tracked evaluation of a large patient cohort. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.
“We developed a simplified scoring system for evaluating risk of thromboembolism and guiding prophylaxis that led to a significant reduction in events across a large integrated health care system,” reported James Wylie, MD, associate medical director for hip and knee preservation and orthopedic research at Intermountain Healthcare, Salt Lake City, Utah.
The goal of the methodology was to create a uniform and evidence-based approach to risk assessment in order to guide selection of appropriate venous thromboembolism (VTE) prophylaxis. The tool takes into account the need to individualize antithrombotic drugs for risk of both VTE and for bleeding.
“VTE is a major threat following total joint replacement, but not all patients require anticoagulants. Recent evidence supports a shift to aspirin for low-risk patients,” explained Dr. Wylie in an interview.
The risk tool assigns points for such factors as history of VTE, older age, history of coronary artery disease, history of cancer, and increased body mass index. There are two possible ratings to guide strategies. Those with standard risk are candidates for 81 mg of aspirin twice daily. Those with high risk are candidates for 2.5 mg of apixaban, also administered twice daily. Custom dosing of warfarin is an alternative for the latter group. Regardless of strategy, prophylaxis is administered for 30 days following arthroplasty
“The risk score is calculated automatically, because you have to click a box in the electronic medical record for all of those factors as part of admission orders,” Dr. Wylie said.
The protocol was introduced in July 2017 and adoption was tracked prospectively over 18 months. In an evaluable cohort of 20,284 patients, PE rates in the 71% of patients adherent to the protocol were compared with the 29% who were not.
Over the observation period, the rates of PE were 0.34% and 0.62% (P = .004) for those adherent and nonadherent, respectively. The rate of unplanned readmissions and death, which were secondary outcomes, were both numerically lower in the group treated by adherent surgeons, but the differences did not reach statistical significance.
Adoption of the protocol by surgeons did increase over the course of the observation period, and this correlated with a decrease in unplanned readmissions. Bleeding-related readmission was a rare event in this analysis and did not significantly increase over time, according to Dr. Wylie.
The risk assessment tool, developed by a multispecialty team at Intermountain Healthcare, was based on a review of hundreds of published papers and guidelines, according to Nathan Momberger, MD, who is the associate medical director of total joint replacement at Intermountain and was a coauthor on this study. A member of the team that developed the risk assessment tool, Dr. Momberger noted that new risk score was developed at a time when clinicians have been moving quickly away from warfarin to direct oral anticoagulants.
“None of our surgeons were using the same VTE prophylaxis when we started this project,” Dr. Momberger said. This was a motivation for developing a systemwide approach. In the 22 participating hospitals, there were 50 surgeons performing total knee arthroplasty and 40 surgeons were performing total hip surgery at the time the new protocol was introduced.
Further analyses will provide a more detailed analysis of the effect of the protocol on other thrombotic events, including deep vein thrombosis, and on cost. Since these data were analyzed, protocol adoption has increased and now exceeds 80%, according to Dr. Wylie.
Although a standardized approach to VTE prophylaxis following total joint arthroplasty is attractive, the ideal strategy remains controversial, according to Sunny Parikh, MD, an orthopedic surgeon affiliated with Colchester (England) General Hospital.
As a coauthor of a recent study that quantified symptomatic VTE rates at his and a neighboring hospital over a 3-year period (BMC Musculoskelet Disord. 2020;21:95), Dr. Parikh reported that VTE rates did not reach zero even with a prolonged course of the low-molecular-weight heparin enoxaparin.
At 90 days, the symptomatic VTE rate was only 0.3% for total knee arthroplasty but reached 1.2% for total hip arthroplasty.
“At the time of this study we were using enoxaparin for 28 days following total hip replacements and for 14 days following total knee replacements,” Dr. Parikh reported. Since this study, his institution has switched to a regimen recommended by the U.K.’s National Institute for Health and Clinical Excellence (NICE).
Under the NICE guidelines, VTE prophylaxis for total hip arthroplasty is 40 mg enoxaparin once daily for 14 days followed by 75 mg aspirin for another 14 days, according to Dr. Parikh. For total knee arthroplasty, the standard regimen is 75 mg aspirin for 14 days.
For those who might not be best managed with the standard approach, “there is no clear guideline.” Rather, in patients with renal or liver impairment, “we discuss the case with the hematology team to adjust the doses,” Dr. Parikh reported.
The advantage of a standardized approach applied to all or most patients is that is eliminates disparities, but Dr. Parikh agreed that risk-adjusted prophylaxis might be warranted for optimal outcomes.
Dr. Wylie reported a financial relationship with Arthrex.
A simple tool to guide choice of antithrombotic therapy following total joint arthroplasty led to a reduction in pulmonary embolism (PE) after being introduced systemwide, according to a prospectively tracked evaluation of a large patient cohort. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.
“We developed a simplified scoring system for evaluating risk of thromboembolism and guiding prophylaxis that led to a significant reduction in events across a large integrated health care system,” reported James Wylie, MD, associate medical director for hip and knee preservation and orthopedic research at Intermountain Healthcare, Salt Lake City, Utah.
The goal of the methodology was to create a uniform and evidence-based approach to risk assessment in order to guide selection of appropriate venous thromboembolism (VTE) prophylaxis. The tool takes into account the need to individualize antithrombotic drugs for risk of both VTE and for bleeding.
“VTE is a major threat following total joint replacement, but not all patients require anticoagulants. Recent evidence supports a shift to aspirin for low-risk patients,” explained Dr. Wylie in an interview.
The risk tool assigns points for such factors as history of VTE, older age, history of coronary artery disease, history of cancer, and increased body mass index. There are two possible ratings to guide strategies. Those with standard risk are candidates for 81 mg of aspirin twice daily. Those with high risk are candidates for 2.5 mg of apixaban, also administered twice daily. Custom dosing of warfarin is an alternative for the latter group. Regardless of strategy, prophylaxis is administered for 30 days following arthroplasty
“The risk score is calculated automatically, because you have to click a box in the electronic medical record for all of those factors as part of admission orders,” Dr. Wylie said.
The protocol was introduced in July 2017 and adoption was tracked prospectively over 18 months. In an evaluable cohort of 20,284 patients, PE rates in the 71% of patients adherent to the protocol were compared with the 29% who were not.
Over the observation period, the rates of PE were 0.34% and 0.62% (P = .004) for those adherent and nonadherent, respectively. The rate of unplanned readmissions and death, which were secondary outcomes, were both numerically lower in the group treated by adherent surgeons, but the differences did not reach statistical significance.
Adoption of the protocol by surgeons did increase over the course of the observation period, and this correlated with a decrease in unplanned readmissions. Bleeding-related readmission was a rare event in this analysis and did not significantly increase over time, according to Dr. Wylie.
The risk assessment tool, developed by a multispecialty team at Intermountain Healthcare, was based on a review of hundreds of published papers and guidelines, according to Nathan Momberger, MD, who is the associate medical director of total joint replacement at Intermountain and was a coauthor on this study. A member of the team that developed the risk assessment tool, Dr. Momberger noted that new risk score was developed at a time when clinicians have been moving quickly away from warfarin to direct oral anticoagulants.
“None of our surgeons were using the same VTE prophylaxis when we started this project,” Dr. Momberger said. This was a motivation for developing a systemwide approach. In the 22 participating hospitals, there were 50 surgeons performing total knee arthroplasty and 40 surgeons were performing total hip surgery at the time the new protocol was introduced.
Further analyses will provide a more detailed analysis of the effect of the protocol on other thrombotic events, including deep vein thrombosis, and on cost. Since these data were analyzed, protocol adoption has increased and now exceeds 80%, according to Dr. Wylie.
Although a standardized approach to VTE prophylaxis following total joint arthroplasty is attractive, the ideal strategy remains controversial, according to Sunny Parikh, MD, an orthopedic surgeon affiliated with Colchester (England) General Hospital.
As a coauthor of a recent study that quantified symptomatic VTE rates at his and a neighboring hospital over a 3-year period (BMC Musculoskelet Disord. 2020;21:95), Dr. Parikh reported that VTE rates did not reach zero even with a prolonged course of the low-molecular-weight heparin enoxaparin.
At 90 days, the symptomatic VTE rate was only 0.3% for total knee arthroplasty but reached 1.2% for total hip arthroplasty.
“At the time of this study we were using enoxaparin for 28 days following total hip replacements and for 14 days following total knee replacements,” Dr. Parikh reported. Since this study, his institution has switched to a regimen recommended by the U.K.’s National Institute for Health and Clinical Excellence (NICE).
Under the NICE guidelines, VTE prophylaxis for total hip arthroplasty is 40 mg enoxaparin once daily for 14 days followed by 75 mg aspirin for another 14 days, according to Dr. Parikh. For total knee arthroplasty, the standard regimen is 75 mg aspirin for 14 days.
For those who might not be best managed with the standard approach, “there is no clear guideline.” Rather, in patients with renal or liver impairment, “we discuss the case with the hematology team to adjust the doses,” Dr. Parikh reported.
The advantage of a standardized approach applied to all or most patients is that is eliminates disparities, but Dr. Parikh agreed that risk-adjusted prophylaxis might be warranted for optimal outcomes.
Dr. Wylie reported a financial relationship with Arthrex.
A simple tool to guide choice of antithrombotic therapy following total joint arthroplasty led to a reduction in pulmonary embolism (PE) after being introduced systemwide, according to a prospectively tracked evaluation of a large patient cohort. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.
“We developed a simplified scoring system for evaluating risk of thromboembolism and guiding prophylaxis that led to a significant reduction in events across a large integrated health care system,” reported James Wylie, MD, associate medical director for hip and knee preservation and orthopedic research at Intermountain Healthcare, Salt Lake City, Utah.
The goal of the methodology was to create a uniform and evidence-based approach to risk assessment in order to guide selection of appropriate venous thromboembolism (VTE) prophylaxis. The tool takes into account the need to individualize antithrombotic drugs for risk of both VTE and for bleeding.
“VTE is a major threat following total joint replacement, but not all patients require anticoagulants. Recent evidence supports a shift to aspirin for low-risk patients,” explained Dr. Wylie in an interview.
The risk tool assigns points for such factors as history of VTE, older age, history of coronary artery disease, history of cancer, and increased body mass index. There are two possible ratings to guide strategies. Those with standard risk are candidates for 81 mg of aspirin twice daily. Those with high risk are candidates for 2.5 mg of apixaban, also administered twice daily. Custom dosing of warfarin is an alternative for the latter group. Regardless of strategy, prophylaxis is administered for 30 days following arthroplasty
“The risk score is calculated automatically, because you have to click a box in the electronic medical record for all of those factors as part of admission orders,” Dr. Wylie said.
The protocol was introduced in July 2017 and adoption was tracked prospectively over 18 months. In an evaluable cohort of 20,284 patients, PE rates in the 71% of patients adherent to the protocol were compared with the 29% who were not.
Over the observation period, the rates of PE were 0.34% and 0.62% (P = .004) for those adherent and nonadherent, respectively. The rate of unplanned readmissions and death, which were secondary outcomes, were both numerically lower in the group treated by adherent surgeons, but the differences did not reach statistical significance.
Adoption of the protocol by surgeons did increase over the course of the observation period, and this correlated with a decrease in unplanned readmissions. Bleeding-related readmission was a rare event in this analysis and did not significantly increase over time, according to Dr. Wylie.
The risk assessment tool, developed by a multispecialty team at Intermountain Healthcare, was based on a review of hundreds of published papers and guidelines, according to Nathan Momberger, MD, who is the associate medical director of total joint replacement at Intermountain and was a coauthor on this study. A member of the team that developed the risk assessment tool, Dr. Momberger noted that new risk score was developed at a time when clinicians have been moving quickly away from warfarin to direct oral anticoagulants.
“None of our surgeons were using the same VTE prophylaxis when we started this project,” Dr. Momberger said. This was a motivation for developing a systemwide approach. In the 22 participating hospitals, there were 50 surgeons performing total knee arthroplasty and 40 surgeons were performing total hip surgery at the time the new protocol was introduced.
Further analyses will provide a more detailed analysis of the effect of the protocol on other thrombotic events, including deep vein thrombosis, and on cost. Since these data were analyzed, protocol adoption has increased and now exceeds 80%, according to Dr. Wylie.
Although a standardized approach to VTE prophylaxis following total joint arthroplasty is attractive, the ideal strategy remains controversial, according to Sunny Parikh, MD, an orthopedic surgeon affiliated with Colchester (England) General Hospital.
As a coauthor of a recent study that quantified symptomatic VTE rates at his and a neighboring hospital over a 3-year period (BMC Musculoskelet Disord. 2020;21:95), Dr. Parikh reported that VTE rates did not reach zero even with a prolonged course of the low-molecular-weight heparin enoxaparin.
At 90 days, the symptomatic VTE rate was only 0.3% for total knee arthroplasty but reached 1.2% for total hip arthroplasty.
“At the time of this study we were using enoxaparin for 28 days following total hip replacements and for 14 days following total knee replacements,” Dr. Parikh reported. Since this study, his institution has switched to a regimen recommended by the U.K.’s National Institute for Health and Clinical Excellence (NICE).
Under the NICE guidelines, VTE prophylaxis for total hip arthroplasty is 40 mg enoxaparin once daily for 14 days followed by 75 mg aspirin for another 14 days, according to Dr. Parikh. For total knee arthroplasty, the standard regimen is 75 mg aspirin for 14 days.
For those who might not be best managed with the standard approach, “there is no clear guideline.” Rather, in patients with renal or liver impairment, “we discuss the case with the hematology team to adjust the doses,” Dr. Parikh reported.
The advantage of a standardized approach applied to all or most patients is that is eliminates disparities, but Dr. Parikh agreed that risk-adjusted prophylaxis might be warranted for optimal outcomes.
Dr. Wylie reported a financial relationship with Arthrex.
REPORTING FROM AAOS 2020
LOTUS: Ipatasertib plus paclitaxel may prolong OS in TNBC
according to final results of the phase 2 LOTUS trial.
The median OS was 25.8 months in patients who received ipatasertib plus paclitaxel and 16.9 months in patients who received paclitaxel plus placebo. Although this difference was not statistically significant, it was “clinically meaningful,” according to Rebecca Dent, MD, of the National Cancer Center Singapore. Dr. Dent presented OS data from the LOTUS trial at the European Society of Medical Oncology: Breast Cancer virtual meeting.
Previously reported data showed a progression-free survival benefit in the ipatasertib arm, compared with the placebo arm – 6.2 months and 4.9 months, respectively (Lancet Oncol. 2017 Oct;18[10]:1360-72). An enhanced effect was noted in patients with PIK3CA/AKT1/PTEN–altered tumors, but the OS data were not mature at the time of that primary analysis.
Patients, treatment, and safety
LOTUS participants had measurable locally advanced/metastatic TNBC that was previously untreated with systemic therapy, and they were stratified by prior adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status.
Patients were randomized 1:1 to receive paclitaxel at a dose of 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle plus either placebo (n = 62) or ipatasertib at a dose of 400 mg on days 1-21 (n = 62).
The safety results didn’t differ between the primary and updated results, Dr. Dent noted.
“What we can say is that the combination is extremely well tolerated, especially when we compare it to other targeted agents targeting this pathway,” she said. “What we do see is noticeable diarrhea ... [and] an increase in sensory neuropathy, which is not entirely unexpected.”
Subsequent systemic anticancer therapy was required in 77% of patients in the ipatasertib arm and 90% of patients in the placebo arm.
OS results
The final OS data show a numerical advantage for patients in the ipatasertib arm compared with the placebo arm. The 1-year OS was 83% in the ipatasertib arm and 68% in the placebo arm. The median OS was 25.8 months and 16.9 months, respectively (stratified hazard ratio, 0.80).
“This is a clinically meaningful improvement of 9 months in overall survival, which is indeed not too dissimilar to what we have seen in patients with PD-L1-positive TNBC who are receiving immune checkpoint inhibition in combination with chemotherapy,” Dr. Dent said.
However, the 95% confidence interval for the stratified OS hazard ratio crossed 1 (0.50-1.28). Therefore, the findings require confirmatory phase 3 trial results, Dr. Dent said.
The OS improvements with ipatasertib were seen “in all biomarker-defined subgroups – PTEN normal or low, PIK3CA/AKT1/PTEN altered or non-altered,” she said. OS benefits were more pronounced in patients with altered PIK3C/AKT1/PTEN status, but the numbers are too small to make definitive conclusions, according to Dr. Dent.
‘Promising’ results, confirmation needed
Invited discussant Suzette Delaloge, MD, head of the breast cancer department at Gustave Roussy, Paris, said the OS findings from LOTUS are “quite promising,” and the safety data are “reassuring.”
The findings are comparable to those of the recently published PAKT trial (J Clin Oncol. 2020 Feb 10;38[5]:423-33), she said, noting that “AKT inhibition in combination with paclitaxel deserves phase 3 development, and this is ongoing in major phase 3 trials.”
Dr. Delaloge also noted that the efficacy may not be limited to PIK3CA/AKT–altered tumors, and given the heterogeneity of TNBC – which may explain the differences seen among various studies – “it is very important that such phase 3 trials ideally involve extensive genomical definitions of tumors so that we understand what it is we are talking about and what is the real effect of the drug.”
“The adequate positioning of AKT inhibition in competition/complementation with other ongoing strategies remains to be defined,” she said. “I think these drugs are ready for translation to early phases.”
Dr. Dent said the results of LOTUS warrant confirmation in the ongoing, randomized phase 3 IPATunity130 trial , in which researchers are evaluating first-line ipatasertib plus paclitaxel for metastatic TNBC. She noted that the small sample sizes and heterogeneity of TNBC among LOTUS participants limited the interpretation of the findings.
In another trial, IPATunity170, researchers are evaluating the first-line role of ipatasertib plus paclitaxel and atezolizumab in locally advanced or metastatic TNBC.
“This is an exciting triplet combination that’s been evaluated already in the phase 1 setting, and now we have a phase 3 study evaluating the triplet,” Dr. Dent said.
The LOTUS trial was funded by Roche/Genentech. Dr. Dent reported receiving honoraria from Roche, Novartis, Lilly, Pfizer, Eisai, Merck, and AstraZeneca. Dr. Delaloge reported personal financial interests in AstraZeneca until 2018 and travel and accommodation support from AstraZeneca, Pfizer, Roche, and Pierre Fabre.
SOURCE: Dent R et al. ESMO Breast Cancer 2020, Abstract 139O
according to final results of the phase 2 LOTUS trial.
The median OS was 25.8 months in patients who received ipatasertib plus paclitaxel and 16.9 months in patients who received paclitaxel plus placebo. Although this difference was not statistically significant, it was “clinically meaningful,” according to Rebecca Dent, MD, of the National Cancer Center Singapore. Dr. Dent presented OS data from the LOTUS trial at the European Society of Medical Oncology: Breast Cancer virtual meeting.
Previously reported data showed a progression-free survival benefit in the ipatasertib arm, compared with the placebo arm – 6.2 months and 4.9 months, respectively (Lancet Oncol. 2017 Oct;18[10]:1360-72). An enhanced effect was noted in patients with PIK3CA/AKT1/PTEN–altered tumors, but the OS data were not mature at the time of that primary analysis.
Patients, treatment, and safety
LOTUS participants had measurable locally advanced/metastatic TNBC that was previously untreated with systemic therapy, and they were stratified by prior adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status.
Patients were randomized 1:1 to receive paclitaxel at a dose of 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle plus either placebo (n = 62) or ipatasertib at a dose of 400 mg on days 1-21 (n = 62).
The safety results didn’t differ between the primary and updated results, Dr. Dent noted.
“What we can say is that the combination is extremely well tolerated, especially when we compare it to other targeted agents targeting this pathway,” she said. “What we do see is noticeable diarrhea ... [and] an increase in sensory neuropathy, which is not entirely unexpected.”
Subsequent systemic anticancer therapy was required in 77% of patients in the ipatasertib arm and 90% of patients in the placebo arm.
OS results
The final OS data show a numerical advantage for patients in the ipatasertib arm compared with the placebo arm. The 1-year OS was 83% in the ipatasertib arm and 68% in the placebo arm. The median OS was 25.8 months and 16.9 months, respectively (stratified hazard ratio, 0.80).
“This is a clinically meaningful improvement of 9 months in overall survival, which is indeed not too dissimilar to what we have seen in patients with PD-L1-positive TNBC who are receiving immune checkpoint inhibition in combination with chemotherapy,” Dr. Dent said.
However, the 95% confidence interval for the stratified OS hazard ratio crossed 1 (0.50-1.28). Therefore, the findings require confirmatory phase 3 trial results, Dr. Dent said.
The OS improvements with ipatasertib were seen “in all biomarker-defined subgroups – PTEN normal or low, PIK3CA/AKT1/PTEN altered or non-altered,” she said. OS benefits were more pronounced in patients with altered PIK3C/AKT1/PTEN status, but the numbers are too small to make definitive conclusions, according to Dr. Dent.
‘Promising’ results, confirmation needed
Invited discussant Suzette Delaloge, MD, head of the breast cancer department at Gustave Roussy, Paris, said the OS findings from LOTUS are “quite promising,” and the safety data are “reassuring.”
The findings are comparable to those of the recently published PAKT trial (J Clin Oncol. 2020 Feb 10;38[5]:423-33), she said, noting that “AKT inhibition in combination with paclitaxel deserves phase 3 development, and this is ongoing in major phase 3 trials.”
Dr. Delaloge also noted that the efficacy may not be limited to PIK3CA/AKT–altered tumors, and given the heterogeneity of TNBC – which may explain the differences seen among various studies – “it is very important that such phase 3 trials ideally involve extensive genomical definitions of tumors so that we understand what it is we are talking about and what is the real effect of the drug.”
“The adequate positioning of AKT inhibition in competition/complementation with other ongoing strategies remains to be defined,” she said. “I think these drugs are ready for translation to early phases.”
Dr. Dent said the results of LOTUS warrant confirmation in the ongoing, randomized phase 3 IPATunity130 trial , in which researchers are evaluating first-line ipatasertib plus paclitaxel for metastatic TNBC. She noted that the small sample sizes and heterogeneity of TNBC among LOTUS participants limited the interpretation of the findings.
In another trial, IPATunity170, researchers are evaluating the first-line role of ipatasertib plus paclitaxel and atezolizumab in locally advanced or metastatic TNBC.
“This is an exciting triplet combination that’s been evaluated already in the phase 1 setting, and now we have a phase 3 study evaluating the triplet,” Dr. Dent said.
The LOTUS trial was funded by Roche/Genentech. Dr. Dent reported receiving honoraria from Roche, Novartis, Lilly, Pfizer, Eisai, Merck, and AstraZeneca. Dr. Delaloge reported personal financial interests in AstraZeneca until 2018 and travel and accommodation support from AstraZeneca, Pfizer, Roche, and Pierre Fabre.
SOURCE: Dent R et al. ESMO Breast Cancer 2020, Abstract 139O
according to final results of the phase 2 LOTUS trial.
The median OS was 25.8 months in patients who received ipatasertib plus paclitaxel and 16.9 months in patients who received paclitaxel plus placebo. Although this difference was not statistically significant, it was “clinically meaningful,” according to Rebecca Dent, MD, of the National Cancer Center Singapore. Dr. Dent presented OS data from the LOTUS trial at the European Society of Medical Oncology: Breast Cancer virtual meeting.
Previously reported data showed a progression-free survival benefit in the ipatasertib arm, compared with the placebo arm – 6.2 months and 4.9 months, respectively (Lancet Oncol. 2017 Oct;18[10]:1360-72). An enhanced effect was noted in patients with PIK3CA/AKT1/PTEN–altered tumors, but the OS data were not mature at the time of that primary analysis.
Patients, treatment, and safety
LOTUS participants had measurable locally advanced/metastatic TNBC that was previously untreated with systemic therapy, and they were stratified by prior adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status.
Patients were randomized 1:1 to receive paclitaxel at a dose of 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle plus either placebo (n = 62) or ipatasertib at a dose of 400 mg on days 1-21 (n = 62).
The safety results didn’t differ between the primary and updated results, Dr. Dent noted.
“What we can say is that the combination is extremely well tolerated, especially when we compare it to other targeted agents targeting this pathway,” she said. “What we do see is noticeable diarrhea ... [and] an increase in sensory neuropathy, which is not entirely unexpected.”
Subsequent systemic anticancer therapy was required in 77% of patients in the ipatasertib arm and 90% of patients in the placebo arm.
OS results
The final OS data show a numerical advantage for patients in the ipatasertib arm compared with the placebo arm. The 1-year OS was 83% in the ipatasertib arm and 68% in the placebo arm. The median OS was 25.8 months and 16.9 months, respectively (stratified hazard ratio, 0.80).
“This is a clinically meaningful improvement of 9 months in overall survival, which is indeed not too dissimilar to what we have seen in patients with PD-L1-positive TNBC who are receiving immune checkpoint inhibition in combination with chemotherapy,” Dr. Dent said.
However, the 95% confidence interval for the stratified OS hazard ratio crossed 1 (0.50-1.28). Therefore, the findings require confirmatory phase 3 trial results, Dr. Dent said.
The OS improvements with ipatasertib were seen “in all biomarker-defined subgroups – PTEN normal or low, PIK3CA/AKT1/PTEN altered or non-altered,” she said. OS benefits were more pronounced in patients with altered PIK3C/AKT1/PTEN status, but the numbers are too small to make definitive conclusions, according to Dr. Dent.
‘Promising’ results, confirmation needed
Invited discussant Suzette Delaloge, MD, head of the breast cancer department at Gustave Roussy, Paris, said the OS findings from LOTUS are “quite promising,” and the safety data are “reassuring.”
The findings are comparable to those of the recently published PAKT trial (J Clin Oncol. 2020 Feb 10;38[5]:423-33), she said, noting that “AKT inhibition in combination with paclitaxel deserves phase 3 development, and this is ongoing in major phase 3 trials.”
Dr. Delaloge also noted that the efficacy may not be limited to PIK3CA/AKT–altered tumors, and given the heterogeneity of TNBC – which may explain the differences seen among various studies – “it is very important that such phase 3 trials ideally involve extensive genomical definitions of tumors so that we understand what it is we are talking about and what is the real effect of the drug.”
“The adequate positioning of AKT inhibition in competition/complementation with other ongoing strategies remains to be defined,” she said. “I think these drugs are ready for translation to early phases.”
Dr. Dent said the results of LOTUS warrant confirmation in the ongoing, randomized phase 3 IPATunity130 trial , in which researchers are evaluating first-line ipatasertib plus paclitaxel for metastatic TNBC. She noted that the small sample sizes and heterogeneity of TNBC among LOTUS participants limited the interpretation of the findings.
In another trial, IPATunity170, researchers are evaluating the first-line role of ipatasertib plus paclitaxel and atezolizumab in locally advanced or metastatic TNBC.
“This is an exciting triplet combination that’s been evaluated already in the phase 1 setting, and now we have a phase 3 study evaluating the triplet,” Dr. Dent said.
The LOTUS trial was funded by Roche/Genentech. Dr. Dent reported receiving honoraria from Roche, Novartis, Lilly, Pfizer, Eisai, Merck, and AstraZeneca. Dr. Delaloge reported personal financial interests in AstraZeneca until 2018 and travel and accommodation support from AstraZeneca, Pfizer, Roche, and Pierre Fabre.
SOURCE: Dent R et al. ESMO Breast Cancer 2020, Abstract 139O
FROM ESMO BREAST CANCER 2020
More from REDUCE-IT: Icosapent ethyl cuts revascularization by a third
A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.
The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.
REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.
The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.
“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.
This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.
“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.
“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.
Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).
Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).
The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”
Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.
REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.
“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.
“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.
Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”
Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”
Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.
A version of this article originally appeared on Medscape.com.
A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.
The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.
REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.
The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.
“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.
This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.
“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.
“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.
Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).
Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).
The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”
Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.
REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.
“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.
“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.
Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”
Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”
Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.
A version of this article originally appeared on Medscape.com.
A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.
The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.
REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.
The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.
“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.
This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.
“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.
“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.
Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).
Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).
The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”
Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.
REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.
“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.
“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.
Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”
Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”
Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.
A version of this article originally appeared on Medscape.com.
Mixed results for aducanumab in two phase 3 trials for Alzheimer’s disease
Aducanumab was associated with favorable changes in activities of daily living and in Alzheimer’s disease biomarkers.
The EMERGE and ENGAGE studies compared low-dose and high-dose aducanumab and placebo over 78 weeks. The high-dose EMERGE cohort experienced a 22% improvement in the primary outcome – adjusted mean Clinical Dementia Rating Sum of Box (CDR-SB) scores – compared with baseline.
“We have with EMERGE, in the high-dose group, a positive result,” said lead author Samantha Budd Haeberlein, PhD, who presented this research online as part of the 2020 American Academy of Neurology Science Highlights.
In contrast, the low-dose EMERGE group, as well as the low-dose and high-dose cohorts in the ENGAGE study, experienced no statistically significant change in CDR-SB outcomes.
Clinical benefit was associated with the degree of exposure to aducanumab. For example, a protocol adjustment during the study increased the mean dose of aducanumab, a move associated with better outcomes.
“We believe that the difference between the results was largely due to patients’ greater exposure to the high dose of aducanumab,” Dr. Haerberlein, senior vice president and head of the neurodegeneration development unit at Biogen in Cambridge, Mass., said in an interview.
Although the studies shared an identical design, “because ENGAGE began enrolling first and recruitment remained ahead of EMERGE, more patients in EMERGE were impacted by the protocol amendments, which we believe resulted in a higher number of patients exposed to the highest dose in EMERGE versus ENGAGE,” Dr. Haerberlein added.
The EMERGE and ENGAGE studies were conducted at 348 sites in 20 countries. The research included a total of 3,285 participants with mild cognitive impairment caused by Alzheimer’s disease or mild Alzheimer’s disease dementia.
The mean age was 70 years, about 52% were women, and slightly more than half had a history of taking medication for Alzheimer’s disease. The mean Mini-Mental State Exam (MMSE) score was 26 at baseline.
Key findings
Dr. Haerberlein and colleagues reported that the 22% decrease in CDR-SB scores in the high-dose EMERGE participants was significant (P = .01). No significant difference emerged, however, in the ENGAGE study, where high-dose participants had a 2% decrease at 78 weeks in CDR-SB scores (P = .83).
The high-dose EMERGE regimen was also associated with an 18% improvement in MMSE scores (P < .05). In the ENGAGE study, the high-dose MMSE scores increased a nonsignificant 3% (P = .81).
The researchers reported no significant differences in the low-dose cohorts in both studies regarding CDR-SB or MMSE scores at week 78, compared with baseline.
They also assessed amyloid using PET scans. Levels remained essentially the same throughout both studies in the placebo participants. In contrast, there was a statistically significant, dose- and time-dependent reduction associated with both low- and high-dose aducanumab.
Aducanumab treatment was associated with significant benefits on measures of cognition and function such as memory, orientation, and language, Dr. Haeberlein said. “Patients also experienced benefits on activities of daily living including conducting personal finances; performing household chores such as cleaning, shopping, and doing laundry; and independently traveling out of the home.”
Furthermore, reductions in the CSF biomarker phospho-tau in the high-dose EMERGE and ENGAGE cohorts were statistically significant. In contrast, changes in total tau were not significant.
The proportion of patients who experienced an adverse event during EMERGE was similar across groups – 92% of the high-dose group, 88% of the low-dose group, and 87% of the placebo cohort. Similar rates were reported in the ENGAGE high-dose, 90%; low-dose, 90%; and placebo cohorts, 86%.
Adverse events reported in more than 10% of participants included headache, nasopharyngitis, and two forms of amyloid-related imaging abnormalities (ARIA), one of which related to edema (ARIA-E) and the other to hemosiderosis (ARIA-H).
Future plans
Going forward, the researchers are conducting a redosing study to offer aducanumab to all participants in the clinical trials. Also, Biogen is completing the filing of a Biologics License Application with the Food and Drug Administration and with regulatory agencies in other countries.
Early identification and treatment of Alzheimer’s disease remains a priority, Dr. Haeberlein said, because it offers an opportunity to begin health measures like exercise, mental activity, and social engagement; allows people more time to plan for the future; and gives families and loved ones’ time to prepare and support each other. From a research perspective, early identification of this population can maximize chances of participation in a clinical trial as well.
Unanswered questions
“Briefly, while both [studies] were looking at aducanumab’s effect on rate of decline across a variety of measures, one statistically showed a positive impact in a subset and the other did not,” Richard J. Caselli, MD, said when asked to comment on the EMERGE and ENGAGE findings. “The subset were the mildest affected patients on the highest dose for the longest time.”
The main difference between the two studies was that one was adequately powered for this subanalysis and the other was not. Even the underpowered subanalysis showed a beneficial trend, added Dr. Caselli, a neurologist at the Mayo Clinic in Phoenix, Arizona.
Dr. Caselli said these findings raise a number of unanswered questions. For example, is a subanalysis valid? Is the degree of improvement clinically meaningful or meaningful enough to justify the anticipated cost of the drug itself – “likely to be very expensive” plus the “cost and hassle” of monthly IV infusions? Is there enough provider and infusion center capacity going forward? What will the reimbursement from third party payers be like?
Biogen sponsored the EMERGE and ENGAGE studies. Dr. Haeberlein is a Biogen employee. Dr. Caselli had no relevant disclosures.
SOURCE: Haeberlein SB et al. AAN 2020, Abstract 46977.
Aducanumab was associated with favorable changes in activities of daily living and in Alzheimer’s disease biomarkers.
The EMERGE and ENGAGE studies compared low-dose and high-dose aducanumab and placebo over 78 weeks. The high-dose EMERGE cohort experienced a 22% improvement in the primary outcome – adjusted mean Clinical Dementia Rating Sum of Box (CDR-SB) scores – compared with baseline.
“We have with EMERGE, in the high-dose group, a positive result,” said lead author Samantha Budd Haeberlein, PhD, who presented this research online as part of the 2020 American Academy of Neurology Science Highlights.
In contrast, the low-dose EMERGE group, as well as the low-dose and high-dose cohorts in the ENGAGE study, experienced no statistically significant change in CDR-SB outcomes.
Clinical benefit was associated with the degree of exposure to aducanumab. For example, a protocol adjustment during the study increased the mean dose of aducanumab, a move associated with better outcomes.
“We believe that the difference between the results was largely due to patients’ greater exposure to the high dose of aducanumab,” Dr. Haerberlein, senior vice president and head of the neurodegeneration development unit at Biogen in Cambridge, Mass., said in an interview.
Although the studies shared an identical design, “because ENGAGE began enrolling first and recruitment remained ahead of EMERGE, more patients in EMERGE were impacted by the protocol amendments, which we believe resulted in a higher number of patients exposed to the highest dose in EMERGE versus ENGAGE,” Dr. Haerberlein added.
The EMERGE and ENGAGE studies were conducted at 348 sites in 20 countries. The research included a total of 3,285 participants with mild cognitive impairment caused by Alzheimer’s disease or mild Alzheimer’s disease dementia.
The mean age was 70 years, about 52% were women, and slightly more than half had a history of taking medication for Alzheimer’s disease. The mean Mini-Mental State Exam (MMSE) score was 26 at baseline.
Key findings
Dr. Haerberlein and colleagues reported that the 22% decrease in CDR-SB scores in the high-dose EMERGE participants was significant (P = .01). No significant difference emerged, however, in the ENGAGE study, where high-dose participants had a 2% decrease at 78 weeks in CDR-SB scores (P = .83).
The high-dose EMERGE regimen was also associated with an 18% improvement in MMSE scores (P < .05). In the ENGAGE study, the high-dose MMSE scores increased a nonsignificant 3% (P = .81).
The researchers reported no significant differences in the low-dose cohorts in both studies regarding CDR-SB or MMSE scores at week 78, compared with baseline.
They also assessed amyloid using PET scans. Levels remained essentially the same throughout both studies in the placebo participants. In contrast, there was a statistically significant, dose- and time-dependent reduction associated with both low- and high-dose aducanumab.
Aducanumab treatment was associated with significant benefits on measures of cognition and function such as memory, orientation, and language, Dr. Haeberlein said. “Patients also experienced benefits on activities of daily living including conducting personal finances; performing household chores such as cleaning, shopping, and doing laundry; and independently traveling out of the home.”
Furthermore, reductions in the CSF biomarker phospho-tau in the high-dose EMERGE and ENGAGE cohorts were statistically significant. In contrast, changes in total tau were not significant.
The proportion of patients who experienced an adverse event during EMERGE was similar across groups – 92% of the high-dose group, 88% of the low-dose group, and 87% of the placebo cohort. Similar rates were reported in the ENGAGE high-dose, 90%; low-dose, 90%; and placebo cohorts, 86%.
Adverse events reported in more than 10% of participants included headache, nasopharyngitis, and two forms of amyloid-related imaging abnormalities (ARIA), one of which related to edema (ARIA-E) and the other to hemosiderosis (ARIA-H).
Future plans
Going forward, the researchers are conducting a redosing study to offer aducanumab to all participants in the clinical trials. Also, Biogen is completing the filing of a Biologics License Application with the Food and Drug Administration and with regulatory agencies in other countries.
Early identification and treatment of Alzheimer’s disease remains a priority, Dr. Haeberlein said, because it offers an opportunity to begin health measures like exercise, mental activity, and social engagement; allows people more time to plan for the future; and gives families and loved ones’ time to prepare and support each other. From a research perspective, early identification of this population can maximize chances of participation in a clinical trial as well.
Unanswered questions
“Briefly, while both [studies] were looking at aducanumab’s effect on rate of decline across a variety of measures, one statistically showed a positive impact in a subset and the other did not,” Richard J. Caselli, MD, said when asked to comment on the EMERGE and ENGAGE findings. “The subset were the mildest affected patients on the highest dose for the longest time.”
The main difference between the two studies was that one was adequately powered for this subanalysis and the other was not. Even the underpowered subanalysis showed a beneficial trend, added Dr. Caselli, a neurologist at the Mayo Clinic in Phoenix, Arizona.
Dr. Caselli said these findings raise a number of unanswered questions. For example, is a subanalysis valid? Is the degree of improvement clinically meaningful or meaningful enough to justify the anticipated cost of the drug itself – “likely to be very expensive” plus the “cost and hassle” of monthly IV infusions? Is there enough provider and infusion center capacity going forward? What will the reimbursement from third party payers be like?
Biogen sponsored the EMERGE and ENGAGE studies. Dr. Haeberlein is a Biogen employee. Dr. Caselli had no relevant disclosures.
SOURCE: Haeberlein SB et al. AAN 2020, Abstract 46977.
Aducanumab was associated with favorable changes in activities of daily living and in Alzheimer’s disease biomarkers.
The EMERGE and ENGAGE studies compared low-dose and high-dose aducanumab and placebo over 78 weeks. The high-dose EMERGE cohort experienced a 22% improvement in the primary outcome – adjusted mean Clinical Dementia Rating Sum of Box (CDR-SB) scores – compared with baseline.
“We have with EMERGE, in the high-dose group, a positive result,” said lead author Samantha Budd Haeberlein, PhD, who presented this research online as part of the 2020 American Academy of Neurology Science Highlights.
In contrast, the low-dose EMERGE group, as well as the low-dose and high-dose cohorts in the ENGAGE study, experienced no statistically significant change in CDR-SB outcomes.
Clinical benefit was associated with the degree of exposure to aducanumab. For example, a protocol adjustment during the study increased the mean dose of aducanumab, a move associated with better outcomes.
“We believe that the difference between the results was largely due to patients’ greater exposure to the high dose of aducanumab,” Dr. Haerberlein, senior vice president and head of the neurodegeneration development unit at Biogen in Cambridge, Mass., said in an interview.
Although the studies shared an identical design, “because ENGAGE began enrolling first and recruitment remained ahead of EMERGE, more patients in EMERGE were impacted by the protocol amendments, which we believe resulted in a higher number of patients exposed to the highest dose in EMERGE versus ENGAGE,” Dr. Haerberlein added.
The EMERGE and ENGAGE studies were conducted at 348 sites in 20 countries. The research included a total of 3,285 participants with mild cognitive impairment caused by Alzheimer’s disease or mild Alzheimer’s disease dementia.
The mean age was 70 years, about 52% were women, and slightly more than half had a history of taking medication for Alzheimer’s disease. The mean Mini-Mental State Exam (MMSE) score was 26 at baseline.
Key findings
Dr. Haerberlein and colleagues reported that the 22% decrease in CDR-SB scores in the high-dose EMERGE participants was significant (P = .01). No significant difference emerged, however, in the ENGAGE study, where high-dose participants had a 2% decrease at 78 weeks in CDR-SB scores (P = .83).
The high-dose EMERGE regimen was also associated with an 18% improvement in MMSE scores (P < .05). In the ENGAGE study, the high-dose MMSE scores increased a nonsignificant 3% (P = .81).
The researchers reported no significant differences in the low-dose cohorts in both studies regarding CDR-SB or MMSE scores at week 78, compared with baseline.
They also assessed amyloid using PET scans. Levels remained essentially the same throughout both studies in the placebo participants. In contrast, there was a statistically significant, dose- and time-dependent reduction associated with both low- and high-dose aducanumab.
Aducanumab treatment was associated with significant benefits on measures of cognition and function such as memory, orientation, and language, Dr. Haeberlein said. “Patients also experienced benefits on activities of daily living including conducting personal finances; performing household chores such as cleaning, shopping, and doing laundry; and independently traveling out of the home.”
Furthermore, reductions in the CSF biomarker phospho-tau in the high-dose EMERGE and ENGAGE cohorts were statistically significant. In contrast, changes in total tau were not significant.
The proportion of patients who experienced an adverse event during EMERGE was similar across groups – 92% of the high-dose group, 88% of the low-dose group, and 87% of the placebo cohort. Similar rates were reported in the ENGAGE high-dose, 90%; low-dose, 90%; and placebo cohorts, 86%.
Adverse events reported in more than 10% of participants included headache, nasopharyngitis, and two forms of amyloid-related imaging abnormalities (ARIA), one of which related to edema (ARIA-E) and the other to hemosiderosis (ARIA-H).
Future plans
Going forward, the researchers are conducting a redosing study to offer aducanumab to all participants in the clinical trials. Also, Biogen is completing the filing of a Biologics License Application with the Food and Drug Administration and with regulatory agencies in other countries.
Early identification and treatment of Alzheimer’s disease remains a priority, Dr. Haeberlein said, because it offers an opportunity to begin health measures like exercise, mental activity, and social engagement; allows people more time to plan for the future; and gives families and loved ones’ time to prepare and support each other. From a research perspective, early identification of this population can maximize chances of participation in a clinical trial as well.
Unanswered questions
“Briefly, while both [studies] were looking at aducanumab’s effect on rate of decline across a variety of measures, one statistically showed a positive impact in a subset and the other did not,” Richard J. Caselli, MD, said when asked to comment on the EMERGE and ENGAGE findings. “The subset were the mildest affected patients on the highest dose for the longest time.”
The main difference between the two studies was that one was adequately powered for this subanalysis and the other was not. Even the underpowered subanalysis showed a beneficial trend, added Dr. Caselli, a neurologist at the Mayo Clinic in Phoenix, Arizona.
Dr. Caselli said these findings raise a number of unanswered questions. For example, is a subanalysis valid? Is the degree of improvement clinically meaningful or meaningful enough to justify the anticipated cost of the drug itself – “likely to be very expensive” plus the “cost and hassle” of monthly IV infusions? Is there enough provider and infusion center capacity going forward? What will the reimbursement from third party payers be like?
Biogen sponsored the EMERGE and ENGAGE studies. Dr. Haeberlein is a Biogen employee. Dr. Caselli had no relevant disclosures.
SOURCE: Haeberlein SB et al. AAN 2020, Abstract 46977.
FROM AAN 2020
Galcanezumab looks promising for treatment-resistant migraine
“The patients included in our study had previously tried multiple migraine preventive treatments that didn’t work for them. These patients are left with limited treatment options to help with the debilitating pain of migraine,” said lead author Holland C. Detke, PhD, senior clinical research advisor at Eli Lilly and Company Biomedicines.
Participants who took the drug experienced “a rapid reduction in migraine days starting as early as month 1, and continuing through the 6 months of the study,” Dr. Detke said.
The treatment group reported an average 4.0 fewer monthly migraine days at 3 months, for example, compared with a baseline of 13.4 days, whereas the placebo group decreased an average 1.29 days from a similar baseline of 13.0 migraine days.
Dr. Detke presented these and other results of the open-label phase of the CONQUER phase 3 trial online as part of the 2020 American Academy of Neurology Science Highlights.
The investigators enrolled 462 adults with episodic or chronic migraine. All participants previously failed two to four migraine treatments because of insufficient efficacy or issues around tolerability or safety. At month 0, 232 people were randomly assigned to galcanezumab and another 230 to placebo injections. At 3 months, 449 participants received a galcanezumab injection as part of the open-label treatment phase.
Participants were an average 48 years old, approximately 86% were women, and 82% were white. At baseline, mean Migraine Specific Quality of Life Role Function Restrictive (MSQ RFR) domain score was 45, “indicating significant impairment in functioning,” Dr. Detke said. At the same time, mean Migraine Disability Assessment Test (MIDAS) total score was 51, “indicating quite severe disability.”
Significant outcomes
The decrease in migraine days at 3 months – 4.0 days with treatment versus 1.29 with placebo – was statistically significant (P < .0001). During the open-label phase, participants who switched from placebo “essentially catch up to where the previously treated people were,” Dr. Detke said. At 6 months, the decrease in average monthly headache days was 5.60 in the initial galcanezumab group versus 5.24 in the initial placebo group.
Significant differences at 3 months versus baseline were observed in participants who received galcanezumab when investigators assessed reduction in 50% or more, 75% or more, or 100% of mean monthly migraine days. No such significant decreases were seen in the placebo group.
Treatment-emergent adverse events reported in the open-label phase included nasopharyngitis in 4.2%, injection site pain in 3.8%, and injection site erythema in 2.7%. Five participants discontinued during the open-label phase because of adverse events.
The results of the study suggest galcanezumab “should be considered as a treatment option for patients who have not had success with previous treatments,” Dr. Detke said.
Multiple strengths of study
“It is encouraging that galcanezumab works in patients who have failed prior reduction strategies,” A. Laine Green, MD, a neurologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., said when asked to comment.
This study did not look at patients who have failed more than four previous reduction strategies, he added. “Clinically we see many of these patients. To be fair, no one has studied this group using the monoclonal antibodies.”
Dr. Green noted several strengths of the study. The groups were similar, there were few dropouts during the open-label extension, and there were no unexpected side effects or adverse events. “Those who got placebo caught up to those who received active treatment in the double-blind phase,” he said. “It is also nice to see patient reported outcomes improved as headaches improve. This adds consistency to the results.”
One caveat, Dr. Green noted, is “with open-label extensions, there is always the potential for bias because patients know what treatment they are receiving.”
Overall [the study] gives hope that patients who have failed previous reduction strategies may respond to the newer monoclonal antibodies.”
Aligns with previous findings
The results are “the same as any other long-term extension study of a drug for migraine,” Stephen Silberstein, MD, said when asked to comment. “The longer one takes it, the better you get.”
The research also confirms that if you switch patients taking placebo to an active treatment, they get better, added Dr. Silberstein, director of the Headache Center at Jefferson Health in Philadelphia.
Because they are injections, agents such as galcanezumab, other monoclonal antibodies, and botulinum toxin offer better compliance for headache compared with small molecule medications that require daily oral dosing, he added.
Eli Lilly and Company funded the study. Dr. Holland Detke is a Lilly employee. Dr. Green collaborated with Lilly on a poster for the AHS scientific meeting on a similar topic but did not receive compensation. Up until August 2019, he served as a consultant for Lilly, Novartis, Teva and Allergan. Dr. Green is also a member of the Medscape and American Headache Society Migraine Steering Committee. Dr. Silberstein is a member of the advisory board and consultant for Lilly.
Source: Detke HC et al. AAN 2020. Abstract 43625.
“The patients included in our study had previously tried multiple migraine preventive treatments that didn’t work for them. These patients are left with limited treatment options to help with the debilitating pain of migraine,” said lead author Holland C. Detke, PhD, senior clinical research advisor at Eli Lilly and Company Biomedicines.
Participants who took the drug experienced “a rapid reduction in migraine days starting as early as month 1, and continuing through the 6 months of the study,” Dr. Detke said.
The treatment group reported an average 4.0 fewer monthly migraine days at 3 months, for example, compared with a baseline of 13.4 days, whereas the placebo group decreased an average 1.29 days from a similar baseline of 13.0 migraine days.
Dr. Detke presented these and other results of the open-label phase of the CONQUER phase 3 trial online as part of the 2020 American Academy of Neurology Science Highlights.
The investigators enrolled 462 adults with episodic or chronic migraine. All participants previously failed two to four migraine treatments because of insufficient efficacy or issues around tolerability or safety. At month 0, 232 people were randomly assigned to galcanezumab and another 230 to placebo injections. At 3 months, 449 participants received a galcanezumab injection as part of the open-label treatment phase.
Participants were an average 48 years old, approximately 86% were women, and 82% were white. At baseline, mean Migraine Specific Quality of Life Role Function Restrictive (MSQ RFR) domain score was 45, “indicating significant impairment in functioning,” Dr. Detke said. At the same time, mean Migraine Disability Assessment Test (MIDAS) total score was 51, “indicating quite severe disability.”
Significant outcomes
The decrease in migraine days at 3 months – 4.0 days with treatment versus 1.29 with placebo – was statistically significant (P < .0001). During the open-label phase, participants who switched from placebo “essentially catch up to where the previously treated people were,” Dr. Detke said. At 6 months, the decrease in average monthly headache days was 5.60 in the initial galcanezumab group versus 5.24 in the initial placebo group.
Significant differences at 3 months versus baseline were observed in participants who received galcanezumab when investigators assessed reduction in 50% or more, 75% or more, or 100% of mean monthly migraine days. No such significant decreases were seen in the placebo group.
Treatment-emergent adverse events reported in the open-label phase included nasopharyngitis in 4.2%, injection site pain in 3.8%, and injection site erythema in 2.7%. Five participants discontinued during the open-label phase because of adverse events.
The results of the study suggest galcanezumab “should be considered as a treatment option for patients who have not had success with previous treatments,” Dr. Detke said.
Multiple strengths of study
“It is encouraging that galcanezumab works in patients who have failed prior reduction strategies,” A. Laine Green, MD, a neurologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., said when asked to comment.
This study did not look at patients who have failed more than four previous reduction strategies, he added. “Clinically we see many of these patients. To be fair, no one has studied this group using the monoclonal antibodies.”
Dr. Green noted several strengths of the study. The groups were similar, there were few dropouts during the open-label extension, and there were no unexpected side effects or adverse events. “Those who got placebo caught up to those who received active treatment in the double-blind phase,” he said. “It is also nice to see patient reported outcomes improved as headaches improve. This adds consistency to the results.”
One caveat, Dr. Green noted, is “with open-label extensions, there is always the potential for bias because patients know what treatment they are receiving.”
Overall [the study] gives hope that patients who have failed previous reduction strategies may respond to the newer monoclonal antibodies.”
Aligns with previous findings
The results are “the same as any other long-term extension study of a drug for migraine,” Stephen Silberstein, MD, said when asked to comment. “The longer one takes it, the better you get.”
The research also confirms that if you switch patients taking placebo to an active treatment, they get better, added Dr. Silberstein, director of the Headache Center at Jefferson Health in Philadelphia.
Because they are injections, agents such as galcanezumab, other monoclonal antibodies, and botulinum toxin offer better compliance for headache compared with small molecule medications that require daily oral dosing, he added.
Eli Lilly and Company funded the study. Dr. Holland Detke is a Lilly employee. Dr. Green collaborated with Lilly on a poster for the AHS scientific meeting on a similar topic but did not receive compensation. Up until August 2019, he served as a consultant for Lilly, Novartis, Teva and Allergan. Dr. Green is also a member of the Medscape and American Headache Society Migraine Steering Committee. Dr. Silberstein is a member of the advisory board and consultant for Lilly.
Source: Detke HC et al. AAN 2020. Abstract 43625.
“The patients included in our study had previously tried multiple migraine preventive treatments that didn’t work for them. These patients are left with limited treatment options to help with the debilitating pain of migraine,” said lead author Holland C. Detke, PhD, senior clinical research advisor at Eli Lilly and Company Biomedicines.
Participants who took the drug experienced “a rapid reduction in migraine days starting as early as month 1, and continuing through the 6 months of the study,” Dr. Detke said.
The treatment group reported an average 4.0 fewer monthly migraine days at 3 months, for example, compared with a baseline of 13.4 days, whereas the placebo group decreased an average 1.29 days from a similar baseline of 13.0 migraine days.
Dr. Detke presented these and other results of the open-label phase of the CONQUER phase 3 trial online as part of the 2020 American Academy of Neurology Science Highlights.
The investigators enrolled 462 adults with episodic or chronic migraine. All participants previously failed two to four migraine treatments because of insufficient efficacy or issues around tolerability or safety. At month 0, 232 people were randomly assigned to galcanezumab and another 230 to placebo injections. At 3 months, 449 participants received a galcanezumab injection as part of the open-label treatment phase.
Participants were an average 48 years old, approximately 86% were women, and 82% were white. At baseline, mean Migraine Specific Quality of Life Role Function Restrictive (MSQ RFR) domain score was 45, “indicating significant impairment in functioning,” Dr. Detke said. At the same time, mean Migraine Disability Assessment Test (MIDAS) total score was 51, “indicating quite severe disability.”
Significant outcomes
The decrease in migraine days at 3 months – 4.0 days with treatment versus 1.29 with placebo – was statistically significant (P < .0001). During the open-label phase, participants who switched from placebo “essentially catch up to where the previously treated people were,” Dr. Detke said. At 6 months, the decrease in average monthly headache days was 5.60 in the initial galcanezumab group versus 5.24 in the initial placebo group.
Significant differences at 3 months versus baseline were observed in participants who received galcanezumab when investigators assessed reduction in 50% or more, 75% or more, or 100% of mean monthly migraine days. No such significant decreases were seen in the placebo group.
Treatment-emergent adverse events reported in the open-label phase included nasopharyngitis in 4.2%, injection site pain in 3.8%, and injection site erythema in 2.7%. Five participants discontinued during the open-label phase because of adverse events.
The results of the study suggest galcanezumab “should be considered as a treatment option for patients who have not had success with previous treatments,” Dr. Detke said.
Multiple strengths of study
“It is encouraging that galcanezumab works in patients who have failed prior reduction strategies,” A. Laine Green, MD, a neurologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., said when asked to comment.
This study did not look at patients who have failed more than four previous reduction strategies, he added. “Clinically we see many of these patients. To be fair, no one has studied this group using the monoclonal antibodies.”
Dr. Green noted several strengths of the study. The groups were similar, there were few dropouts during the open-label extension, and there were no unexpected side effects or adverse events. “Those who got placebo caught up to those who received active treatment in the double-blind phase,” he said. “It is also nice to see patient reported outcomes improved as headaches improve. This adds consistency to the results.”
One caveat, Dr. Green noted, is “with open-label extensions, there is always the potential for bias because patients know what treatment they are receiving.”
Overall [the study] gives hope that patients who have failed previous reduction strategies may respond to the newer monoclonal antibodies.”
Aligns with previous findings
The results are “the same as any other long-term extension study of a drug for migraine,” Stephen Silberstein, MD, said when asked to comment. “The longer one takes it, the better you get.”
The research also confirms that if you switch patients taking placebo to an active treatment, they get better, added Dr. Silberstein, director of the Headache Center at Jefferson Health in Philadelphia.
Because they are injections, agents such as galcanezumab, other monoclonal antibodies, and botulinum toxin offer better compliance for headache compared with small molecule medications that require daily oral dosing, he added.
Eli Lilly and Company funded the study. Dr. Holland Detke is a Lilly employee. Dr. Green collaborated with Lilly on a poster for the AHS scientific meeting on a similar topic but did not receive compensation. Up until August 2019, he served as a consultant for Lilly, Novartis, Teva and Allergan. Dr. Green is also a member of the Medscape and American Headache Society Migraine Steering Committee. Dr. Silberstein is a member of the advisory board and consultant for Lilly.
Source: Detke HC et al. AAN 2020. Abstract 43625.
FROM AAN 2020
Chronic migraine is associated with changes in the amygdala
, according to researchers. This increased connectivity is associated with clinical and affective measures. The data suggest that changes in the amygdala’s structure and function may play a role in the transformation to chronic migraine, according to the researchers. The study was presented online as part of the American Academy of Neurology’s 2020 Science Highlights.
Approximately 3% of patients with episodic migraine progress to chronic migraine each year. Chronic migraine is associated with increased headache frequency, greater disability, and increased psychiatric comorbidities. The pathophysiological mechanisms of the transformation from episodic to chronic migraine are not completely understood.
Danielle D. DeSouza, PhD, instructor in neurology at Stanford (Calif.) University, and colleagues sought to investigate the role of the amygdala in the transformation of migraine. The amygdala is involved in nociceptive processing, emotional responses, and affective states such as depression and anxiety. Researchers have suggested that alterations in the structure or function of the amygdala might contribute to the worsening of pain and mood that coincides with the transformation of migraine.
Dr. DeSouza and colleagues enrolled 88 patients with migraine, diagnosed according to International Classification of Headache Disorders–3 criteria, in their study. Forty-four patients (36 women; mean age, 37.8 years) had chronic migraine, and 44 patients (36 women; mean age, 37.5 years) had episodic migraine. Participants underwent 3T MRI scanning during which investigators acquired T1-weighted structural and resting-state images of the brain. Participants also completed self-report questionnaires to evaluate depression and somatization (Patient Health Questionnaire), anxiety (Generalized Anxiety Disorder 7-item scale), pain catastrophizing (Pain Catastrophizing Scale), headache frequency, and headache intensity.
The investigators examined resting-state functional connectivity between the amygdala and the following three brain networks: DMN, salience network (SN), and central executive network (CEN). They assessed amygdala volume with voxel-based morphometry.
Analyses indicated that connectivity between the left amygdala and the DMN (i.e., the medial prefrontal cortex and the precuneus/posterior cingulate cortex) was increased in patients with chronic migraine, compared with those with episodic migraine. In all patients, resting-state functional connectivity between the amygdala and the DMN was positively associated with headache frequency. Connectivity between the left amygdala and the SN was positively associated with headache intensity, and connectivity between the right amygdala and the CEN was positively associated with pain catastrophizing. Both of these findings held in all patients.
In addition, Dr. DeSouza and colleagues found that bilateral amygdala volumes, including the basolateral and superficial/corticoid nuclei, were increased in patients with chronic migraine, compared with those with episodic migraine. Headache intensity and depression predicted differences in right amygdala volume, and depression alone predicted differences in left amygdala volume.
Dr. DeSouza reported no disclosures. One of the investigators acts as an adviser to Alder, Allergan, Amgen, Biohaven, Curex, Teva, and Xoc about matters unrelated to this study.
SOURCE: DeSouza DD et al. AAN 2020, Abstract 46914.
, according to researchers. This increased connectivity is associated with clinical and affective measures. The data suggest that changes in the amygdala’s structure and function may play a role in the transformation to chronic migraine, according to the researchers. The study was presented online as part of the American Academy of Neurology’s 2020 Science Highlights.
Approximately 3% of patients with episodic migraine progress to chronic migraine each year. Chronic migraine is associated with increased headache frequency, greater disability, and increased psychiatric comorbidities. The pathophysiological mechanisms of the transformation from episodic to chronic migraine are not completely understood.
Danielle D. DeSouza, PhD, instructor in neurology at Stanford (Calif.) University, and colleagues sought to investigate the role of the amygdala in the transformation of migraine. The amygdala is involved in nociceptive processing, emotional responses, and affective states such as depression and anxiety. Researchers have suggested that alterations in the structure or function of the amygdala might contribute to the worsening of pain and mood that coincides with the transformation of migraine.
Dr. DeSouza and colleagues enrolled 88 patients with migraine, diagnosed according to International Classification of Headache Disorders–3 criteria, in their study. Forty-four patients (36 women; mean age, 37.8 years) had chronic migraine, and 44 patients (36 women; mean age, 37.5 years) had episodic migraine. Participants underwent 3T MRI scanning during which investigators acquired T1-weighted structural and resting-state images of the brain. Participants also completed self-report questionnaires to evaluate depression and somatization (Patient Health Questionnaire), anxiety (Generalized Anxiety Disorder 7-item scale), pain catastrophizing (Pain Catastrophizing Scale), headache frequency, and headache intensity.
The investigators examined resting-state functional connectivity between the amygdala and the following three brain networks: DMN, salience network (SN), and central executive network (CEN). They assessed amygdala volume with voxel-based morphometry.
Analyses indicated that connectivity between the left amygdala and the DMN (i.e., the medial prefrontal cortex and the precuneus/posterior cingulate cortex) was increased in patients with chronic migraine, compared with those with episodic migraine. In all patients, resting-state functional connectivity between the amygdala and the DMN was positively associated with headache frequency. Connectivity between the left amygdala and the SN was positively associated with headache intensity, and connectivity between the right amygdala and the CEN was positively associated with pain catastrophizing. Both of these findings held in all patients.
In addition, Dr. DeSouza and colleagues found that bilateral amygdala volumes, including the basolateral and superficial/corticoid nuclei, were increased in patients with chronic migraine, compared with those with episodic migraine. Headache intensity and depression predicted differences in right amygdala volume, and depression alone predicted differences in left amygdala volume.
Dr. DeSouza reported no disclosures. One of the investigators acts as an adviser to Alder, Allergan, Amgen, Biohaven, Curex, Teva, and Xoc about matters unrelated to this study.
SOURCE: DeSouza DD et al. AAN 2020, Abstract 46914.
, according to researchers. This increased connectivity is associated with clinical and affective measures. The data suggest that changes in the amygdala’s structure and function may play a role in the transformation to chronic migraine, according to the researchers. The study was presented online as part of the American Academy of Neurology’s 2020 Science Highlights.
Approximately 3% of patients with episodic migraine progress to chronic migraine each year. Chronic migraine is associated with increased headache frequency, greater disability, and increased psychiatric comorbidities. The pathophysiological mechanisms of the transformation from episodic to chronic migraine are not completely understood.
Danielle D. DeSouza, PhD, instructor in neurology at Stanford (Calif.) University, and colleagues sought to investigate the role of the amygdala in the transformation of migraine. The amygdala is involved in nociceptive processing, emotional responses, and affective states such as depression and anxiety. Researchers have suggested that alterations in the structure or function of the amygdala might contribute to the worsening of pain and mood that coincides with the transformation of migraine.
Dr. DeSouza and colleagues enrolled 88 patients with migraine, diagnosed according to International Classification of Headache Disorders–3 criteria, in their study. Forty-four patients (36 women; mean age, 37.8 years) had chronic migraine, and 44 patients (36 women; mean age, 37.5 years) had episodic migraine. Participants underwent 3T MRI scanning during which investigators acquired T1-weighted structural and resting-state images of the brain. Participants also completed self-report questionnaires to evaluate depression and somatization (Patient Health Questionnaire), anxiety (Generalized Anxiety Disorder 7-item scale), pain catastrophizing (Pain Catastrophizing Scale), headache frequency, and headache intensity.
The investigators examined resting-state functional connectivity between the amygdala and the following three brain networks: DMN, salience network (SN), and central executive network (CEN). They assessed amygdala volume with voxel-based morphometry.
Analyses indicated that connectivity between the left amygdala and the DMN (i.e., the medial prefrontal cortex and the precuneus/posterior cingulate cortex) was increased in patients with chronic migraine, compared with those with episodic migraine. In all patients, resting-state functional connectivity between the amygdala and the DMN was positively associated with headache frequency. Connectivity between the left amygdala and the SN was positively associated with headache intensity, and connectivity between the right amygdala and the CEN was positively associated with pain catastrophizing. Both of these findings held in all patients.
In addition, Dr. DeSouza and colleagues found that bilateral amygdala volumes, including the basolateral and superficial/corticoid nuclei, were increased in patients with chronic migraine, compared with those with episodic migraine. Headache intensity and depression predicted differences in right amygdala volume, and depression alone predicted differences in left amygdala volume.
Dr. DeSouza reported no disclosures. One of the investigators acts as an adviser to Alder, Allergan, Amgen, Biohaven, Curex, Teva, and Xoc about matters unrelated to this study.
SOURCE: DeSouza DD et al. AAN 2020, Abstract 46914.
FROM AAN 2020
Robotic and manual total knee arthroplasty found at least comparable
When results in a series of robotic-assisted total knee arthroplasties (TKA) were compared with a series of arthroplasties performed manually by the same surgeon, results were comparable even though the robotic procedures included a learning phase. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.
“Robotics appears to level the playing field for those who are less experienced, so that robotic total knee arthroplasty might be particularly well suited to low-volume surgeons,” reported Sridhar R. Rachala, MD, assistant professor of orthopaedic surgery, University of Buffalo (N.Y.).
In this retrospective cohort study, radiographic and clinical outcomes were evaluated in 164 total knee arthroplasties performed manually over an 8-month period and compared with 300 procedures performed robotically by the same experienced surgeon over the subsequent 15-month period.
There were no significant differences between patient groups for mean age or body mass index. Dr. Rachala, who performed both sets of procedures, reported inherent differences in technique. Specifically, the mechanical alignment was planned for a traditional neutral mechanical axis, while the robotic procedures were planned in kinematic alignment.
When evaluated at 1 year, the mean KOOS JR (Knee Injury and Osteoarthritis Outcome for Joint Replacement) scores were not significantly different for the robotic and manually performed procedures (76.0 vs. 73.9; P = .54). There were also no differences in the final extension (P = .64) or flexion (P = .59).
However, the difference in mean length of stay (2.0 vs. 2.4 days; P = .0002) favored the robotic approach, and the higher proportion of patients discharged to home after robotic surgery (73% vs. 66%; P = .11) suggested a favorable trend. Planned and postoperative alignment was within two degrees for both groups and not significantly different.
“The robotic series were at a disadvantage because it included cases that I performed when first switching to this approach,” reported Dr. Rachala in an interview.
Although a growing number of total hip arthroplasties are performed robotically, there have not so far been many comparisons of clinical outcomes among surgeons experienced with both approaches, according to Dr. Rachala. Acknowledging that a single-surgeon experience could be considered a limitation of this series, Dr. Rachala also considers it a potential strength. Dr. Rachala was highly experienced with manually instrumented total knee arthroplasty when he switched.
“Positioning and alignment are not just more accurate but easier to perform with robotic assistance,” he said, explaining why this approach is likely to offer a particular advantage to surgeons who perform these types of arthroplasties at low volume. He noted that robotic programming helps prevent errors and adopt alternative more personalized alignments.
Although Dr. Rachala acknowledged that long-term and controlled studies are needed, his experience suggests that robotic-assisted procedures are emerging as a viable alternative with advantages for the surgeon as well as the patient.
The principle that robotic assistance can add consistency to total joint arthroplasty is valid, according to Gwo-Chin Lee, MD, an associate professor of orthopaedic surgery, University of Pennsylvania, Philadelphia. “Robotic-assisted arthroplasty improves the accuracy and consistency of the procedure, which can potentially reduce the likelihood of failure. In knees, it is proven to be valuable in unicompartmental replacements in which results are correlated to a surgeon’s surgical volume. It has an equalizing effect relative to a surgeon with more extensive experience,” Dr. Lee said.
The senior author of a recent systematic review and meta-analysis of robotic-assisted unicompartmental knee arthroplasty (J Knee Surg. 2020 Jan 30; doi: 10.1055/s-0040-1701455), Dr. Lee said, “While the impact of robotics on other metrics including patient satisfaction and early recovery continues to be debated among surgeons who specialize in total knee arthroplasties, the technology can aid surgeons in component position, sizing, and ligament balance, particularly for the lower-volume surgeons and ultimately lead to more predictable outcomes.”
Dr. Rachala reports a financial relationship with Avanos and Stryker.
SOURCE: Rachala S et al. AAOS 2020. Abstract P0091.
When results in a series of robotic-assisted total knee arthroplasties (TKA) were compared with a series of arthroplasties performed manually by the same surgeon, results were comparable even though the robotic procedures included a learning phase. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.
“Robotics appears to level the playing field for those who are less experienced, so that robotic total knee arthroplasty might be particularly well suited to low-volume surgeons,” reported Sridhar R. Rachala, MD, assistant professor of orthopaedic surgery, University of Buffalo (N.Y.).
In this retrospective cohort study, radiographic and clinical outcomes were evaluated in 164 total knee arthroplasties performed manually over an 8-month period and compared with 300 procedures performed robotically by the same experienced surgeon over the subsequent 15-month period.
There were no significant differences between patient groups for mean age or body mass index. Dr. Rachala, who performed both sets of procedures, reported inherent differences in technique. Specifically, the mechanical alignment was planned for a traditional neutral mechanical axis, while the robotic procedures were planned in kinematic alignment.
When evaluated at 1 year, the mean KOOS JR (Knee Injury and Osteoarthritis Outcome for Joint Replacement) scores were not significantly different for the robotic and manually performed procedures (76.0 vs. 73.9; P = .54). There were also no differences in the final extension (P = .64) or flexion (P = .59).
However, the difference in mean length of stay (2.0 vs. 2.4 days; P = .0002) favored the robotic approach, and the higher proportion of patients discharged to home after robotic surgery (73% vs. 66%; P = .11) suggested a favorable trend. Planned and postoperative alignment was within two degrees for both groups and not significantly different.
“The robotic series were at a disadvantage because it included cases that I performed when first switching to this approach,” reported Dr. Rachala in an interview.
Although a growing number of total hip arthroplasties are performed robotically, there have not so far been many comparisons of clinical outcomes among surgeons experienced with both approaches, according to Dr. Rachala. Acknowledging that a single-surgeon experience could be considered a limitation of this series, Dr. Rachala also considers it a potential strength. Dr. Rachala was highly experienced with manually instrumented total knee arthroplasty when he switched.
“Positioning and alignment are not just more accurate but easier to perform with robotic assistance,” he said, explaining why this approach is likely to offer a particular advantage to surgeons who perform these types of arthroplasties at low volume. He noted that robotic programming helps prevent errors and adopt alternative more personalized alignments.
Although Dr. Rachala acknowledged that long-term and controlled studies are needed, his experience suggests that robotic-assisted procedures are emerging as a viable alternative with advantages for the surgeon as well as the patient.
The principle that robotic assistance can add consistency to total joint arthroplasty is valid, according to Gwo-Chin Lee, MD, an associate professor of orthopaedic surgery, University of Pennsylvania, Philadelphia. “Robotic-assisted arthroplasty improves the accuracy and consistency of the procedure, which can potentially reduce the likelihood of failure. In knees, it is proven to be valuable in unicompartmental replacements in which results are correlated to a surgeon’s surgical volume. It has an equalizing effect relative to a surgeon with more extensive experience,” Dr. Lee said.
The senior author of a recent systematic review and meta-analysis of robotic-assisted unicompartmental knee arthroplasty (J Knee Surg. 2020 Jan 30; doi: 10.1055/s-0040-1701455), Dr. Lee said, “While the impact of robotics on other metrics including patient satisfaction and early recovery continues to be debated among surgeons who specialize in total knee arthroplasties, the technology can aid surgeons in component position, sizing, and ligament balance, particularly for the lower-volume surgeons and ultimately lead to more predictable outcomes.”
Dr. Rachala reports a financial relationship with Avanos and Stryker.
SOURCE: Rachala S et al. AAOS 2020. Abstract P0091.
When results in a series of robotic-assisted total knee arthroplasties (TKA) were compared with a series of arthroplasties performed manually by the same surgeon, results were comparable even though the robotic procedures included a learning phase. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.
“Robotics appears to level the playing field for those who are less experienced, so that robotic total knee arthroplasty might be particularly well suited to low-volume surgeons,” reported Sridhar R. Rachala, MD, assistant professor of orthopaedic surgery, University of Buffalo (N.Y.).
In this retrospective cohort study, radiographic and clinical outcomes were evaluated in 164 total knee arthroplasties performed manually over an 8-month period and compared with 300 procedures performed robotically by the same experienced surgeon over the subsequent 15-month period.
There were no significant differences between patient groups for mean age or body mass index. Dr. Rachala, who performed both sets of procedures, reported inherent differences in technique. Specifically, the mechanical alignment was planned for a traditional neutral mechanical axis, while the robotic procedures were planned in kinematic alignment.
When evaluated at 1 year, the mean KOOS JR (Knee Injury and Osteoarthritis Outcome for Joint Replacement) scores were not significantly different for the robotic and manually performed procedures (76.0 vs. 73.9; P = .54). There were also no differences in the final extension (P = .64) or flexion (P = .59).
However, the difference in mean length of stay (2.0 vs. 2.4 days; P = .0002) favored the robotic approach, and the higher proportion of patients discharged to home after robotic surgery (73% vs. 66%; P = .11) suggested a favorable trend. Planned and postoperative alignment was within two degrees for both groups and not significantly different.
“The robotic series were at a disadvantage because it included cases that I performed when first switching to this approach,” reported Dr. Rachala in an interview.
Although a growing number of total hip arthroplasties are performed robotically, there have not so far been many comparisons of clinical outcomes among surgeons experienced with both approaches, according to Dr. Rachala. Acknowledging that a single-surgeon experience could be considered a limitation of this series, Dr. Rachala also considers it a potential strength. Dr. Rachala was highly experienced with manually instrumented total knee arthroplasty when he switched.
“Positioning and alignment are not just more accurate but easier to perform with robotic assistance,” he said, explaining why this approach is likely to offer a particular advantage to surgeons who perform these types of arthroplasties at low volume. He noted that robotic programming helps prevent errors and adopt alternative more personalized alignments.
Although Dr. Rachala acknowledged that long-term and controlled studies are needed, his experience suggests that robotic-assisted procedures are emerging as a viable alternative with advantages for the surgeon as well as the patient.
The principle that robotic assistance can add consistency to total joint arthroplasty is valid, according to Gwo-Chin Lee, MD, an associate professor of orthopaedic surgery, University of Pennsylvania, Philadelphia. “Robotic-assisted arthroplasty improves the accuracy and consistency of the procedure, which can potentially reduce the likelihood of failure. In knees, it is proven to be valuable in unicompartmental replacements in which results are correlated to a surgeon’s surgical volume. It has an equalizing effect relative to a surgeon with more extensive experience,” Dr. Lee said.
The senior author of a recent systematic review and meta-analysis of robotic-assisted unicompartmental knee arthroplasty (J Knee Surg. 2020 Jan 30; doi: 10.1055/s-0040-1701455), Dr. Lee said, “While the impact of robotics on other metrics including patient satisfaction and early recovery continues to be debated among surgeons who specialize in total knee arthroplasties, the technology can aid surgeons in component position, sizing, and ligament balance, particularly for the lower-volume surgeons and ultimately lead to more predictable outcomes.”
Dr. Rachala reports a financial relationship with Avanos and Stryker.
SOURCE: Rachala S et al. AAOS 2020. Abstract P0091.
FROM aaos 2020
COVID-19: Psychiatrists assess geriatric harm from social distancing
One of the greatest tragedies of the first wave of the COVID-19 pandemic has been the failure of health policy makers to anticipate and mitigate the enormous havoc the policy of social distancing would wreak on mental health and cognitive function in older persons, speakers agreed at a webinar on COVID-19, social distancing, and its impact on social and mental health in the elderly hosted by the International Psychogeriatric Association in collaboration with INTERDEM.
“Social distancing” is a two-edged sword: It is for now and the foreseeable future the only available effective strategy for protecting against infection in the older population most vulnerable to severe forms of COVID-19. Yet social distancing also has caused many elderly – particularly those in nursing homes and other long-term care facilities – to plunge into a profound experience of loneliness, isolation, distress, feelings of abandonment, anxiety, depression, and accelerated cognitive deterioration. And this needn’t have happened, the mental health professionals asserted.
“When are we going to get rid of the term ‘social distancing?’ ” asked IPA President William E. Reichman, MD. “Many have appreciated – including the World Health Organization – that the real issue is physical distancing to prevent contagion. And physical distancing doesn’t have to mean social distancing.”
Social connectedness between elderly persons and their peers and family members can be maintained and should be emphatically encouraged during the physical distancing required by the pandemic, said Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers.
This can be achieved using readily available technologies, including the telephone and videoconferencing, as well as by creating opportunities for supervised masked visits between a family member and an elderly loved one in outdoor courtyards or gardens within long-term care facilities. And yet, as the pandemic seized hold in many parts of the world, family members were blocked from entry to these facilities, she observed.
Impact on mental health, cognition
Dr. Vernooij-Dassen noted that studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly.
“ Conversely, epidemiologic data indicate that a socially integrated lifestyle had a favorable influence on cognitive functioning and could even delay onset of dementia,” she said.
INTERDEM is backing two ongoing studies evaluating the hypothesis that interventions fostering increased social interaction among elderly individuals can delay onset of dementia or favorably affect its course. The proposed mechanism of benefit is stimulation of brain plasticity to enhance cognitive reserve.
“This is a hypothesis of hope. We know that social interaction for humans is like water to plants – we really, really need it,” she explained.
Diego de Leo, MD, PhD, emeritus professor of psychiatry and former director of the Australian Institute for Suicide Research and Prevention at Griffith University in Brisbane, was living in hard-hit Padua, Italy, during the first surge of COVID-19. He described his anecdotal experience.
“What I hear from many Italian colleagues and friends and directors of mental health services is that emergency admissions related to mental disorders declined during the first wave of the COVID pandemic. For example, not many people attended emergency departments due to suicide attempts; there was a very marked decrease in the number of suicide attempts during the worst days of the pandemic,” he said.
People with psychiatric conditions were afraid to go to the hospital because they thought they would contract the infection and die there. That’s changing now, however.
“Now there is an increased number of admissions to mental health units. A new wave. It has been a U-shaped curve. And we’re now witnessing an increasing number of fatal suicides due to persistent fears, due to people imagining that there is no more room for them, and no more future for them from a financial point of view – which is the major negative outcome of this crisis. It will be a disaster for many families,” the psychiatrist continued.
A noteworthy phenomenon in northern Italy was that, when tablets were made available to nursing home residents in an effort to enhance their connectedness to the outside world, those with dementia often became so frustrated and confused by their difficulty in using the devices that they developed a hypokinetic delirium marked by refusal to eat or leave their bed, he reported.
It’s far too early to have reliable data on suicide trends in response to the pandemic, according to Dr. de Leo. But one thing is for sure: The strategy of social distancing employed to curb COVID-19 has increased the prevalence of known risk factors for suicide in older individuals, including loneliness, anxiety, and depression; increased alcohol use; and a perception of being a burden on society. Dr. de Leo directs a foundation dedicated to helping people experiencing traumatic bereavement, and in one recent week, the foundation was contacted by eight families in the province of Padua with a recent death by suicide apparently related to fallout from the COVID-19 pandemic. That’s an unusually high spike in suicide in a province with a population of 1 million.
“People probably preferred to end the agitation, the fear, the extreme anxiety about their destiny by deciding to prematurely truncate their life. That has been reported by nursing staff,” he said.
The Italian government has determined that, to date, 36% of all COVID-related deaths have occurred in people aged 85 years or older, and 84% of deaths were in individuals aged at least 70 years. And in Milan and the surrounding province of Lombardy, it’s estimated that COVID-19 has taken the lives of 25% of all nursing home residents. The North American experience has been uncomfortably similar.
“Almost 80% of COVID deaths in Canada have occurred in congregate settings,” observed Dr. Reichman, professor of psychiatry at the University of Toronto, and president and CEO of Baycrest Health Sciences, a geriatric research center.
“Certainly, the appalling number of deaths in nursing homes is the No. 1 horror of the pandemic,” declared Carmelle Peisah, MBBS, MD, a psychiatrist at the University of New South Wales in Kensington, Australia.
The fire next time
The conventional wisdom holds that COVID-19 has caused all sorts of mayhem in the delivery of elder care. Not so, in Dr. Reichman’s view.
“I would suggest that the pandemic has not caused many of the problems we talk about, it’s actually revealed problems that have always been there under the surface. For example, many older people, even before COVID-19, were socially isolated, socially distant. They had difficulty connecting with their relatives, difficulty accessing transportation to get to the store to buy food and see their doctors, and to interact with other older people,” the psychiatrist said.
“I would say as well that the pandemic didn’t cause the problems we’ve seen in long-term congregate senior care. The pandemic revealed them. We’ve had facilities where older people were severely crowded together, which compromises their quality of life, even when there’s not a pandemic. We’ve had difficulty staffing these kinds of environments with people that are paid an honest wage for the very hard work that they do. In many of these settings they’re inadequately trained, not only in infection prevention and control but in all other aspects of care. And the pandemic has revealed that many of these organizations are not properly funded. The government doesn’t support them well enough across jurisdictions, and they can’t raise enough philanthropic funds to provide the kind of quality of life that residents demand,” Dr. Reichman continued.
Could the pandemic spur improved elder care? His hope is that health care professionals, politicians, and society at large will learn from the devastation left by the first surge of the pandemic and will lobby for the resources necessary for much-needed improvements in geriatric care.
“We need to be better prepared should there be not only a second wave of this pandemic, but for other pandemics to come,” Dr. Reichman concluded.
The speakers indicated they had no financial conflicts regarding their presentations.
One of the greatest tragedies of the first wave of the COVID-19 pandemic has been the failure of health policy makers to anticipate and mitigate the enormous havoc the policy of social distancing would wreak on mental health and cognitive function in older persons, speakers agreed at a webinar on COVID-19, social distancing, and its impact on social and mental health in the elderly hosted by the International Psychogeriatric Association in collaboration with INTERDEM.
“Social distancing” is a two-edged sword: It is for now and the foreseeable future the only available effective strategy for protecting against infection in the older population most vulnerable to severe forms of COVID-19. Yet social distancing also has caused many elderly – particularly those in nursing homes and other long-term care facilities – to plunge into a profound experience of loneliness, isolation, distress, feelings of abandonment, anxiety, depression, and accelerated cognitive deterioration. And this needn’t have happened, the mental health professionals asserted.
“When are we going to get rid of the term ‘social distancing?’ ” asked IPA President William E. Reichman, MD. “Many have appreciated – including the World Health Organization – that the real issue is physical distancing to prevent contagion. And physical distancing doesn’t have to mean social distancing.”
Social connectedness between elderly persons and their peers and family members can be maintained and should be emphatically encouraged during the physical distancing required by the pandemic, said Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers.
This can be achieved using readily available technologies, including the telephone and videoconferencing, as well as by creating opportunities for supervised masked visits between a family member and an elderly loved one in outdoor courtyards or gardens within long-term care facilities. And yet, as the pandemic seized hold in many parts of the world, family members were blocked from entry to these facilities, she observed.
Impact on mental health, cognition
Dr. Vernooij-Dassen noted that studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly.
“ Conversely, epidemiologic data indicate that a socially integrated lifestyle had a favorable influence on cognitive functioning and could even delay onset of dementia,” she said.
INTERDEM is backing two ongoing studies evaluating the hypothesis that interventions fostering increased social interaction among elderly individuals can delay onset of dementia or favorably affect its course. The proposed mechanism of benefit is stimulation of brain plasticity to enhance cognitive reserve.
“This is a hypothesis of hope. We know that social interaction for humans is like water to plants – we really, really need it,” she explained.
Diego de Leo, MD, PhD, emeritus professor of psychiatry and former director of the Australian Institute for Suicide Research and Prevention at Griffith University in Brisbane, was living in hard-hit Padua, Italy, during the first surge of COVID-19. He described his anecdotal experience.
“What I hear from many Italian colleagues and friends and directors of mental health services is that emergency admissions related to mental disorders declined during the first wave of the COVID pandemic. For example, not many people attended emergency departments due to suicide attempts; there was a very marked decrease in the number of suicide attempts during the worst days of the pandemic,” he said.
People with psychiatric conditions were afraid to go to the hospital because they thought they would contract the infection and die there. That’s changing now, however.
“Now there is an increased number of admissions to mental health units. A new wave. It has been a U-shaped curve. And we’re now witnessing an increasing number of fatal suicides due to persistent fears, due to people imagining that there is no more room for them, and no more future for them from a financial point of view – which is the major negative outcome of this crisis. It will be a disaster for many families,” the psychiatrist continued.
A noteworthy phenomenon in northern Italy was that, when tablets were made available to nursing home residents in an effort to enhance their connectedness to the outside world, those with dementia often became so frustrated and confused by their difficulty in using the devices that they developed a hypokinetic delirium marked by refusal to eat or leave their bed, he reported.
It’s far too early to have reliable data on suicide trends in response to the pandemic, according to Dr. de Leo. But one thing is for sure: The strategy of social distancing employed to curb COVID-19 has increased the prevalence of known risk factors for suicide in older individuals, including loneliness, anxiety, and depression; increased alcohol use; and a perception of being a burden on society. Dr. de Leo directs a foundation dedicated to helping people experiencing traumatic bereavement, and in one recent week, the foundation was contacted by eight families in the province of Padua with a recent death by suicide apparently related to fallout from the COVID-19 pandemic. That’s an unusually high spike in suicide in a province with a population of 1 million.
“People probably preferred to end the agitation, the fear, the extreme anxiety about their destiny by deciding to prematurely truncate their life. That has been reported by nursing staff,” he said.
The Italian government has determined that, to date, 36% of all COVID-related deaths have occurred in people aged 85 years or older, and 84% of deaths were in individuals aged at least 70 years. And in Milan and the surrounding province of Lombardy, it’s estimated that COVID-19 has taken the lives of 25% of all nursing home residents. The North American experience has been uncomfortably similar.
“Almost 80% of COVID deaths in Canada have occurred in congregate settings,” observed Dr. Reichman, professor of psychiatry at the University of Toronto, and president and CEO of Baycrest Health Sciences, a geriatric research center.
“Certainly, the appalling number of deaths in nursing homes is the No. 1 horror of the pandemic,” declared Carmelle Peisah, MBBS, MD, a psychiatrist at the University of New South Wales in Kensington, Australia.
The fire next time
The conventional wisdom holds that COVID-19 has caused all sorts of mayhem in the delivery of elder care. Not so, in Dr. Reichman’s view.
“I would suggest that the pandemic has not caused many of the problems we talk about, it’s actually revealed problems that have always been there under the surface. For example, many older people, even before COVID-19, were socially isolated, socially distant. They had difficulty connecting with their relatives, difficulty accessing transportation to get to the store to buy food and see their doctors, and to interact with other older people,” the psychiatrist said.
“I would say as well that the pandemic didn’t cause the problems we’ve seen in long-term congregate senior care. The pandemic revealed them. We’ve had facilities where older people were severely crowded together, which compromises their quality of life, even when there’s not a pandemic. We’ve had difficulty staffing these kinds of environments with people that are paid an honest wage for the very hard work that they do. In many of these settings they’re inadequately trained, not only in infection prevention and control but in all other aspects of care. And the pandemic has revealed that many of these organizations are not properly funded. The government doesn’t support them well enough across jurisdictions, and they can’t raise enough philanthropic funds to provide the kind of quality of life that residents demand,” Dr. Reichman continued.
Could the pandemic spur improved elder care? His hope is that health care professionals, politicians, and society at large will learn from the devastation left by the first surge of the pandemic and will lobby for the resources necessary for much-needed improvements in geriatric care.
“We need to be better prepared should there be not only a second wave of this pandemic, but for other pandemics to come,” Dr. Reichman concluded.
The speakers indicated they had no financial conflicts regarding their presentations.
One of the greatest tragedies of the first wave of the COVID-19 pandemic has been the failure of health policy makers to anticipate and mitigate the enormous havoc the policy of social distancing would wreak on mental health and cognitive function in older persons, speakers agreed at a webinar on COVID-19, social distancing, and its impact on social and mental health in the elderly hosted by the International Psychogeriatric Association in collaboration with INTERDEM.
“Social distancing” is a two-edged sword: It is for now and the foreseeable future the only available effective strategy for protecting against infection in the older population most vulnerable to severe forms of COVID-19. Yet social distancing also has caused many elderly – particularly those in nursing homes and other long-term care facilities – to plunge into a profound experience of loneliness, isolation, distress, feelings of abandonment, anxiety, depression, and accelerated cognitive deterioration. And this needn’t have happened, the mental health professionals asserted.
“When are we going to get rid of the term ‘social distancing?’ ” asked IPA President William E. Reichman, MD. “Many have appreciated – including the World Health Organization – that the real issue is physical distancing to prevent contagion. And physical distancing doesn’t have to mean social distancing.”
Social connectedness between elderly persons and their peers and family members can be maintained and should be emphatically encouraged during the physical distancing required by the pandemic, said Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers.
This can be achieved using readily available technologies, including the telephone and videoconferencing, as well as by creating opportunities for supervised masked visits between a family member and an elderly loved one in outdoor courtyards or gardens within long-term care facilities. And yet, as the pandemic seized hold in many parts of the world, family members were blocked from entry to these facilities, she observed.
Impact on mental health, cognition
Dr. Vernooij-Dassen noted that studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly.
“ Conversely, epidemiologic data indicate that a socially integrated lifestyle had a favorable influence on cognitive functioning and could even delay onset of dementia,” she said.
INTERDEM is backing two ongoing studies evaluating the hypothesis that interventions fostering increased social interaction among elderly individuals can delay onset of dementia or favorably affect its course. The proposed mechanism of benefit is stimulation of brain plasticity to enhance cognitive reserve.
“This is a hypothesis of hope. We know that social interaction for humans is like water to plants – we really, really need it,” she explained.
Diego de Leo, MD, PhD, emeritus professor of psychiatry and former director of the Australian Institute for Suicide Research and Prevention at Griffith University in Brisbane, was living in hard-hit Padua, Italy, during the first surge of COVID-19. He described his anecdotal experience.
“What I hear from many Italian colleagues and friends and directors of mental health services is that emergency admissions related to mental disorders declined during the first wave of the COVID pandemic. For example, not many people attended emergency departments due to suicide attempts; there was a very marked decrease in the number of suicide attempts during the worst days of the pandemic,” he said.
People with psychiatric conditions were afraid to go to the hospital because they thought they would contract the infection and die there. That’s changing now, however.
“Now there is an increased number of admissions to mental health units. A new wave. It has been a U-shaped curve. And we’re now witnessing an increasing number of fatal suicides due to persistent fears, due to people imagining that there is no more room for them, and no more future for them from a financial point of view – which is the major negative outcome of this crisis. It will be a disaster for many families,” the psychiatrist continued.
A noteworthy phenomenon in northern Italy was that, when tablets were made available to nursing home residents in an effort to enhance their connectedness to the outside world, those with dementia often became so frustrated and confused by their difficulty in using the devices that they developed a hypokinetic delirium marked by refusal to eat or leave their bed, he reported.
It’s far too early to have reliable data on suicide trends in response to the pandemic, according to Dr. de Leo. But one thing is for sure: The strategy of social distancing employed to curb COVID-19 has increased the prevalence of known risk factors for suicide in older individuals, including loneliness, anxiety, and depression; increased alcohol use; and a perception of being a burden on society. Dr. de Leo directs a foundation dedicated to helping people experiencing traumatic bereavement, and in one recent week, the foundation was contacted by eight families in the province of Padua with a recent death by suicide apparently related to fallout from the COVID-19 pandemic. That’s an unusually high spike in suicide in a province with a population of 1 million.
“People probably preferred to end the agitation, the fear, the extreme anxiety about their destiny by deciding to prematurely truncate their life. That has been reported by nursing staff,” he said.
The Italian government has determined that, to date, 36% of all COVID-related deaths have occurred in people aged 85 years or older, and 84% of deaths were in individuals aged at least 70 years. And in Milan and the surrounding province of Lombardy, it’s estimated that COVID-19 has taken the lives of 25% of all nursing home residents. The North American experience has been uncomfortably similar.
“Almost 80% of COVID deaths in Canada have occurred in congregate settings,” observed Dr. Reichman, professor of psychiatry at the University of Toronto, and president and CEO of Baycrest Health Sciences, a geriatric research center.
“Certainly, the appalling number of deaths in nursing homes is the No. 1 horror of the pandemic,” declared Carmelle Peisah, MBBS, MD, a psychiatrist at the University of New South Wales in Kensington, Australia.
The fire next time
The conventional wisdom holds that COVID-19 has caused all sorts of mayhem in the delivery of elder care. Not so, in Dr. Reichman’s view.
“I would suggest that the pandemic has not caused many of the problems we talk about, it’s actually revealed problems that have always been there under the surface. For example, many older people, even before COVID-19, were socially isolated, socially distant. They had difficulty connecting with their relatives, difficulty accessing transportation to get to the store to buy food and see their doctors, and to interact with other older people,” the psychiatrist said.
“I would say as well that the pandemic didn’t cause the problems we’ve seen in long-term congregate senior care. The pandemic revealed them. We’ve had facilities where older people were severely crowded together, which compromises their quality of life, even when there’s not a pandemic. We’ve had difficulty staffing these kinds of environments with people that are paid an honest wage for the very hard work that they do. In many of these settings they’re inadequately trained, not only in infection prevention and control but in all other aspects of care. And the pandemic has revealed that many of these organizations are not properly funded. The government doesn’t support them well enough across jurisdictions, and they can’t raise enough philanthropic funds to provide the kind of quality of life that residents demand,” Dr. Reichman continued.
Could the pandemic spur improved elder care? His hope is that health care professionals, politicians, and society at large will learn from the devastation left by the first surge of the pandemic and will lobby for the resources necessary for much-needed improvements in geriatric care.
“We need to be better prepared should there be not only a second wave of this pandemic, but for other pandemics to come,” Dr. Reichman concluded.
The speakers indicated they had no financial conflicts regarding their presentations.