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TKA outcomes for age 80+ similar to younger patients
CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.
Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.
Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.
Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.
Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).
Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.
Reassuring older patients
However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).
“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”
These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.
The number of total knee replacements is expected to rise dramatically in the United States.
In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”
Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”
He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.
In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).
Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.
The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.
A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.
“It’s a small and manageable risk if you pick the right patients,” he said.
Demand for TKAs rises as population ages
As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.
“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.
This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.
“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”
Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.
Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.
Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.
Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.
Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).
Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.
Reassuring older patients
However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).
“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”
These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.
The number of total knee replacements is expected to rise dramatically in the United States.
In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”
Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”
He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.
In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).
Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.
The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.
A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.
“It’s a small and manageable risk if you pick the right patients,” he said.
Demand for TKAs rises as population ages
As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.
“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.
This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.
“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”
Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.
Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.
Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.
Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.
Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).
Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.
Reassuring older patients
However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).
“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”
These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.
The number of total knee replacements is expected to rise dramatically in the United States.
In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”
Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”
He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.
In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).
Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.
The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.
A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.
“It’s a small and manageable risk if you pick the right patients,” he said.
Demand for TKAs rises as population ages
As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.
“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.
This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.
“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”
Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Aducanumab and ARIA: Does the FDA’s prescribing label put patients at risk?
Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.
“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.
Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
Significant safety risk?
As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.
ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.
ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.
Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.
A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.
“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.
Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.
The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.
Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.
Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.
The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.
Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.
Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.
Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
Four cases
Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.
“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.
Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”
In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.
Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.
“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.
Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”
None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”
“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.
The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.
“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.
Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
Significant safety risk?
As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.
ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.
ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.
Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.
A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.
“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.
Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.
The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.
Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.
Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.
The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.
Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.
Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.
Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
Four cases
Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.
“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.
Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”
In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.
Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.
“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.
Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”
None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”
“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.
The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.
“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.
Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
Significant safety risk?
As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.
ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.
ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.
Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.
A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.
“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.
Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.
The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.
Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.
Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.
The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.
Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.
Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.
Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
Four cases
Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.
“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.
Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”
In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.
Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.
“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.
Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”
None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”
“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.
The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAGP 2022
Using a Real-Time Prediction Algorithm to Improve Sleep in the Hospital
Study Overview
Objective: This study evaluated whether a clinical-decision-support (CDS) tool that utilizes a real-time algorithm incorporating patient vital sign data can identify hospitalized patients who can forgo overnight vital sign checks and thus reduce delirium incidence.
Design: This was a parallel randomized clinical trial of adult inpatients admitted to the general medical service of a tertiary care academic medical center in the United States. The trial intervention consisted of a CDS notification in the electronic health record (EHR) that informed the physician if a patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model of real-time patient data input. This notification provided the physician an opportunity to discontinue nighttime vital sign checks, dismiss the notification for 1 hour, or dismiss the notification until the next day.
Setting and participants: This clinical trial was conducted at the University of California, San Francisco Medical Center from March 11 to November 24, 2019. Participants included physicians who served on the primary team (eg, attending, resident) of 1699 patients on the general medical service who were outside of the intensive care unit (ICU). The hospital encounters were randomized (allocation ratio of 1:1) to sleep promotion vitals CDS (SPV CDS) intervention or usual care.
Main outcome and measures: The primary outcome was delirium as determined by bedside nurse assessment using the Nursing Delirium Screening Scale (Nu-DESC) recorded once per nursing shift. The Nu-DESC is a standardized delirium screening tool that defines delirium with a score ≥2. Secondary outcomes included sleep opportunity (ie, EHR-based sleep metrics that reflected the maximum time between iatrogenic interruptions, such as nighttime vital sign checks) and patient satisfaction (ie, patient satisfaction measured by standardized Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS] survey). Potential balancing outcomes were assessed to ensure that reduced vital sign checks were not causing harms; these included ICU transfers, rapid response calls, and code blue alarms. All analyses were conducted on the basis of intention-to-treat.
Main results: A total of 3025 inpatient encounters were screened and 1930 encounters were randomized (966 SPV CDS intervention; 964 usual care). The randomized encounters consisted of 1699 patients; demographic factors between the 2 trial arms were similar. Specifically, the intervention arm included 566 men (59%) and mean (SD) age was 53 (15) years. The incidence of delirium was similar between the intervention and usual care arms: 108 (11%) vs 123 (13%) (P = .32). Compared to the usual care arm, the intervention arm had a higher mean (SD) number of sleep opportunity hours per night (4.95 [1.45] vs 4.57 [1.30], P < .001) and fewer nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86], P < .001). The post-discharge HCAHPS survey measuring patient satisfaction was completed by only 5% of patients (53 intervention, 49 usual care), and survey results were similar between the 2 arms (P = .86). In addition, safety outcomes including ICU transfers (49 [5%] vs 47 [5%], P = .92), rapid response calls (68 [7%] vs 55 [6%], P = .27), and code blue alarms (2 [0.2%] vs 9 [0.9%], P = .07) were similar between the study arms.
Conclusion: In this randomized clinical trial, a CDS tool utilizing a real-time prediction algorithm embedded in EHR did not reduce the incidence of delirium in hospitalized patients. However, this SPV CDS intervention helped physicians identify clinically stable patients who can forgo routine nighttime vital sign checks and facilitated greater opportunity for patients to sleep. These findings suggest that augmenting physician judgment using a real-time prediction algorithm can help to improve sleep opportunity without an accompanying increased risk of clinical decompensation during acute care.
Commentary
High-quality sleep is fundamental to health and well-being. Sleep deprivation and disorders are associated with many adverse health outcomes, including increased risks for obesity, diabetes, hypertension, myocardial infarction, and depression.1 In hospitalized patients who are acutely ill, restorative sleep is critical to facilitating recovery. However, poor sleep is exceedingly common in hospitalized patients and is associated with deleterious outcomes, such as high blood pressure, hyperglycemia, and delirium.2,3 Moreover, some of these adverse sleep-induced cardiometabolic outcomes, as well as sleep disruption itself, may persist after hospital discharge.4 Factors that precipitate interrupted sleep during hospitalization include iatrogenic causes such as frequent vital sign checks, nighttime procedures or early morning blood draws, and environmental factors such as loud ambient noise.3 Thus, a potential intervention to improve sleep quality in the hospital is to reduce nighttime interruptions such as frequent vital sign checks.
In the current study, Najafi and colleagues conducted a randomized trial to evaluate whether a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, can be utilized to identify patients in whom vital sign checks can be safely discontinued at nighttime. The authors found a modest but statistically significant reduction in the number of nighttime vital sign checks in patients who underwent the SPV CDS intervention, and a corresponding higher sleep opportunity per night in those who received the intervention. Importantly, this reduction in nighttime vital sign checks did not cause a higher risk of clinical decompensation as measured by ICU transfers, rapid response calls, or code blue alarms. Thus, the results demonstrated the feasibility of using a real-time, patient data-driven CDS tool to augment physician judgment in managing sleep disruption, an important hospital-associated stressor and a common hazard of hospitalization in older patients.
Delirium is a common clinical problem in hospitalized older patients that is associated with prolonged hospitalization, functional and cognitive decline, institutionalization, death, and increased health care costs.5 Despite a potential benefit of SPV CDS intervention in reducing vital sign checks and increasing sleep opportunity, this intervention did not reduce the incidence of delirium in hospitalized patients. This finding is not surprising given that delirium has a multifactorial etiology (eg, metabolic derangements, infections, medication side effects and drug toxicity, hospital environment). A small modification in nighttime vital sign checks and sleep opportunity may have limited impact on optimizing sleep quality and does not address other risk factors for delirium. As such, a multicomponent nonpharmacologic approach that includes sleep enhancement, early mobilization, feeding assistance, fluid repletion, infection prevention, and other interventions should guide delirium prevention in the hospital setting. The SPV CDS intervention may play a role in the delivery of a multifaceted, nonpharmacologic delirium prevention intervention in high-risk individuals.
Sleep disruption is one of the multiple hazards of hospitalization frequently experience by hospitalized older patients. Other hazards, or hospital-associated stressors, include mobility restriction (eg, physical restraints such as urinary catheters and intravenous lines, bed elevation and rails), malnourishment and dehydration (eg, frequent use of no-food-by-mouth order, lack of easy access to hydration), and pain (eg, poor pain control). Extended exposures to these stressors may lead to a maladaptive state called allostatic overload that transiently increases vulnerability to post-hospitalization adverse events, including emergency department use, hospital readmission, or death (ie, post-hospital syndrome).6 Thus, the optimization of sleep during hospitalization in vulnerable patients may have benefits that extend beyond delirium prevention. It is perceivable that a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, may be applied to reduce some of these hazards of hospitalization in addition to improving sleep opportunity.
Applications for Clinical Practice
Findings from the current study indicate that a CDS tool embedded in EHR that utilizes a real-time prediction algorithm of patient data may help to safely improve sleep opportunity in hospitalized patients. The participants in the current study were relatively young (53 [15] years). Given that age is a risk factor for delirium, the effects of this intervention on delirium prevention in the most susceptible population (ie, those over the age of 65) remain unknown and further investigation is warranted. Additional studies are needed to determine whether this approach yields similar results in geriatric patients and improves clinical outcomes.
—Fred Ko, MD
1. Institute of Medicine (US) Committee on Sleep Medicine and Research. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Colten HR, Altevogt BM, editors. National Academies Press (US); 2006.
2. Pilkington S. Causes and consequences of sleep deprivation in hospitalised patients. Nurs Stand. 2013;27(49):350-342. doi:10.7748/ns2013.08.27.49.35.e7649
3. Stewart NH, Arora VM. Sleep in hospitalized older adults. Sleep Med Clin. 2018;13(1):127-135. doi:10.1016/j.jsmc.2017.09.012
4. Altman MT, Knauert MP, Pisani MA. Sleep disturbance after hospitalization and critical illness: a systematic review. Ann Am Thorac Soc. 2017;14(9):1457-1468. doi:10.1513/AnnalsATS.201702-148SR
5. Oh ES, Fong TG, Hshieh TT, Inouye SK. Delirium in older persons: advances in diagnosis and treatment. JAMA. 2017;318(12):1161-1174. doi:10.1001/jama.2017.12067
6. Goldwater DS, Dharmarajan K, McEwan BS, Krumholz HM. Is posthospital syndrome a result of hospitalization-induced allostatic overload? J Hosp Med. 2018;13(5). doi:10.12788/jhm.2986
Study Overview
Objective: This study evaluated whether a clinical-decision-support (CDS) tool that utilizes a real-time algorithm incorporating patient vital sign data can identify hospitalized patients who can forgo overnight vital sign checks and thus reduce delirium incidence.
Design: This was a parallel randomized clinical trial of adult inpatients admitted to the general medical service of a tertiary care academic medical center in the United States. The trial intervention consisted of a CDS notification in the electronic health record (EHR) that informed the physician if a patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model of real-time patient data input. This notification provided the physician an opportunity to discontinue nighttime vital sign checks, dismiss the notification for 1 hour, or dismiss the notification until the next day.
Setting and participants: This clinical trial was conducted at the University of California, San Francisco Medical Center from March 11 to November 24, 2019. Participants included physicians who served on the primary team (eg, attending, resident) of 1699 patients on the general medical service who were outside of the intensive care unit (ICU). The hospital encounters were randomized (allocation ratio of 1:1) to sleep promotion vitals CDS (SPV CDS) intervention or usual care.
Main outcome and measures: The primary outcome was delirium as determined by bedside nurse assessment using the Nursing Delirium Screening Scale (Nu-DESC) recorded once per nursing shift. The Nu-DESC is a standardized delirium screening tool that defines delirium with a score ≥2. Secondary outcomes included sleep opportunity (ie, EHR-based sleep metrics that reflected the maximum time between iatrogenic interruptions, such as nighttime vital sign checks) and patient satisfaction (ie, patient satisfaction measured by standardized Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS] survey). Potential balancing outcomes were assessed to ensure that reduced vital sign checks were not causing harms; these included ICU transfers, rapid response calls, and code blue alarms. All analyses were conducted on the basis of intention-to-treat.
Main results: A total of 3025 inpatient encounters were screened and 1930 encounters were randomized (966 SPV CDS intervention; 964 usual care). The randomized encounters consisted of 1699 patients; demographic factors between the 2 trial arms were similar. Specifically, the intervention arm included 566 men (59%) and mean (SD) age was 53 (15) years. The incidence of delirium was similar between the intervention and usual care arms: 108 (11%) vs 123 (13%) (P = .32). Compared to the usual care arm, the intervention arm had a higher mean (SD) number of sleep opportunity hours per night (4.95 [1.45] vs 4.57 [1.30], P < .001) and fewer nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86], P < .001). The post-discharge HCAHPS survey measuring patient satisfaction was completed by only 5% of patients (53 intervention, 49 usual care), and survey results were similar between the 2 arms (P = .86). In addition, safety outcomes including ICU transfers (49 [5%] vs 47 [5%], P = .92), rapid response calls (68 [7%] vs 55 [6%], P = .27), and code blue alarms (2 [0.2%] vs 9 [0.9%], P = .07) were similar between the study arms.
Conclusion: In this randomized clinical trial, a CDS tool utilizing a real-time prediction algorithm embedded in EHR did not reduce the incidence of delirium in hospitalized patients. However, this SPV CDS intervention helped physicians identify clinically stable patients who can forgo routine nighttime vital sign checks and facilitated greater opportunity for patients to sleep. These findings suggest that augmenting physician judgment using a real-time prediction algorithm can help to improve sleep opportunity without an accompanying increased risk of clinical decompensation during acute care.
Commentary
High-quality sleep is fundamental to health and well-being. Sleep deprivation and disorders are associated with many adverse health outcomes, including increased risks for obesity, diabetes, hypertension, myocardial infarction, and depression.1 In hospitalized patients who are acutely ill, restorative sleep is critical to facilitating recovery. However, poor sleep is exceedingly common in hospitalized patients and is associated with deleterious outcomes, such as high blood pressure, hyperglycemia, and delirium.2,3 Moreover, some of these adverse sleep-induced cardiometabolic outcomes, as well as sleep disruption itself, may persist after hospital discharge.4 Factors that precipitate interrupted sleep during hospitalization include iatrogenic causes such as frequent vital sign checks, nighttime procedures or early morning blood draws, and environmental factors such as loud ambient noise.3 Thus, a potential intervention to improve sleep quality in the hospital is to reduce nighttime interruptions such as frequent vital sign checks.
In the current study, Najafi and colleagues conducted a randomized trial to evaluate whether a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, can be utilized to identify patients in whom vital sign checks can be safely discontinued at nighttime. The authors found a modest but statistically significant reduction in the number of nighttime vital sign checks in patients who underwent the SPV CDS intervention, and a corresponding higher sleep opportunity per night in those who received the intervention. Importantly, this reduction in nighttime vital sign checks did not cause a higher risk of clinical decompensation as measured by ICU transfers, rapid response calls, or code blue alarms. Thus, the results demonstrated the feasibility of using a real-time, patient data-driven CDS tool to augment physician judgment in managing sleep disruption, an important hospital-associated stressor and a common hazard of hospitalization in older patients.
Delirium is a common clinical problem in hospitalized older patients that is associated with prolonged hospitalization, functional and cognitive decline, institutionalization, death, and increased health care costs.5 Despite a potential benefit of SPV CDS intervention in reducing vital sign checks and increasing sleep opportunity, this intervention did not reduce the incidence of delirium in hospitalized patients. This finding is not surprising given that delirium has a multifactorial etiology (eg, metabolic derangements, infections, medication side effects and drug toxicity, hospital environment). A small modification in nighttime vital sign checks and sleep opportunity may have limited impact on optimizing sleep quality and does not address other risk factors for delirium. As such, a multicomponent nonpharmacologic approach that includes sleep enhancement, early mobilization, feeding assistance, fluid repletion, infection prevention, and other interventions should guide delirium prevention in the hospital setting. The SPV CDS intervention may play a role in the delivery of a multifaceted, nonpharmacologic delirium prevention intervention in high-risk individuals.
Sleep disruption is one of the multiple hazards of hospitalization frequently experience by hospitalized older patients. Other hazards, or hospital-associated stressors, include mobility restriction (eg, physical restraints such as urinary catheters and intravenous lines, bed elevation and rails), malnourishment and dehydration (eg, frequent use of no-food-by-mouth order, lack of easy access to hydration), and pain (eg, poor pain control). Extended exposures to these stressors may lead to a maladaptive state called allostatic overload that transiently increases vulnerability to post-hospitalization adverse events, including emergency department use, hospital readmission, or death (ie, post-hospital syndrome).6 Thus, the optimization of sleep during hospitalization in vulnerable patients may have benefits that extend beyond delirium prevention. It is perceivable that a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, may be applied to reduce some of these hazards of hospitalization in addition to improving sleep opportunity.
Applications for Clinical Practice
Findings from the current study indicate that a CDS tool embedded in EHR that utilizes a real-time prediction algorithm of patient data may help to safely improve sleep opportunity in hospitalized patients. The participants in the current study were relatively young (53 [15] years). Given that age is a risk factor for delirium, the effects of this intervention on delirium prevention in the most susceptible population (ie, those over the age of 65) remain unknown and further investigation is warranted. Additional studies are needed to determine whether this approach yields similar results in geriatric patients and improves clinical outcomes.
—Fred Ko, MD
Study Overview
Objective: This study evaluated whether a clinical-decision-support (CDS) tool that utilizes a real-time algorithm incorporating patient vital sign data can identify hospitalized patients who can forgo overnight vital sign checks and thus reduce delirium incidence.
Design: This was a parallel randomized clinical trial of adult inpatients admitted to the general medical service of a tertiary care academic medical center in the United States. The trial intervention consisted of a CDS notification in the electronic health record (EHR) that informed the physician if a patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model of real-time patient data input. This notification provided the physician an opportunity to discontinue nighttime vital sign checks, dismiss the notification for 1 hour, or dismiss the notification until the next day.
Setting and participants: This clinical trial was conducted at the University of California, San Francisco Medical Center from March 11 to November 24, 2019. Participants included physicians who served on the primary team (eg, attending, resident) of 1699 patients on the general medical service who were outside of the intensive care unit (ICU). The hospital encounters were randomized (allocation ratio of 1:1) to sleep promotion vitals CDS (SPV CDS) intervention or usual care.
Main outcome and measures: The primary outcome was delirium as determined by bedside nurse assessment using the Nursing Delirium Screening Scale (Nu-DESC) recorded once per nursing shift. The Nu-DESC is a standardized delirium screening tool that defines delirium with a score ≥2. Secondary outcomes included sleep opportunity (ie, EHR-based sleep metrics that reflected the maximum time between iatrogenic interruptions, such as nighttime vital sign checks) and patient satisfaction (ie, patient satisfaction measured by standardized Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS] survey). Potential balancing outcomes were assessed to ensure that reduced vital sign checks were not causing harms; these included ICU transfers, rapid response calls, and code blue alarms. All analyses were conducted on the basis of intention-to-treat.
Main results: A total of 3025 inpatient encounters were screened and 1930 encounters were randomized (966 SPV CDS intervention; 964 usual care). The randomized encounters consisted of 1699 patients; demographic factors between the 2 trial arms were similar. Specifically, the intervention arm included 566 men (59%) and mean (SD) age was 53 (15) years. The incidence of delirium was similar between the intervention and usual care arms: 108 (11%) vs 123 (13%) (P = .32). Compared to the usual care arm, the intervention arm had a higher mean (SD) number of sleep opportunity hours per night (4.95 [1.45] vs 4.57 [1.30], P < .001) and fewer nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86], P < .001). The post-discharge HCAHPS survey measuring patient satisfaction was completed by only 5% of patients (53 intervention, 49 usual care), and survey results were similar between the 2 arms (P = .86). In addition, safety outcomes including ICU transfers (49 [5%] vs 47 [5%], P = .92), rapid response calls (68 [7%] vs 55 [6%], P = .27), and code blue alarms (2 [0.2%] vs 9 [0.9%], P = .07) were similar between the study arms.
Conclusion: In this randomized clinical trial, a CDS tool utilizing a real-time prediction algorithm embedded in EHR did not reduce the incidence of delirium in hospitalized patients. However, this SPV CDS intervention helped physicians identify clinically stable patients who can forgo routine nighttime vital sign checks and facilitated greater opportunity for patients to sleep. These findings suggest that augmenting physician judgment using a real-time prediction algorithm can help to improve sleep opportunity without an accompanying increased risk of clinical decompensation during acute care.
Commentary
High-quality sleep is fundamental to health and well-being. Sleep deprivation and disorders are associated with many adverse health outcomes, including increased risks for obesity, diabetes, hypertension, myocardial infarction, and depression.1 In hospitalized patients who are acutely ill, restorative sleep is critical to facilitating recovery. However, poor sleep is exceedingly common in hospitalized patients and is associated with deleterious outcomes, such as high blood pressure, hyperglycemia, and delirium.2,3 Moreover, some of these adverse sleep-induced cardiometabolic outcomes, as well as sleep disruption itself, may persist after hospital discharge.4 Factors that precipitate interrupted sleep during hospitalization include iatrogenic causes such as frequent vital sign checks, nighttime procedures or early morning blood draws, and environmental factors such as loud ambient noise.3 Thus, a potential intervention to improve sleep quality in the hospital is to reduce nighttime interruptions such as frequent vital sign checks.
In the current study, Najafi and colleagues conducted a randomized trial to evaluate whether a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, can be utilized to identify patients in whom vital sign checks can be safely discontinued at nighttime. The authors found a modest but statistically significant reduction in the number of nighttime vital sign checks in patients who underwent the SPV CDS intervention, and a corresponding higher sleep opportunity per night in those who received the intervention. Importantly, this reduction in nighttime vital sign checks did not cause a higher risk of clinical decompensation as measured by ICU transfers, rapid response calls, or code blue alarms. Thus, the results demonstrated the feasibility of using a real-time, patient data-driven CDS tool to augment physician judgment in managing sleep disruption, an important hospital-associated stressor and a common hazard of hospitalization in older patients.
Delirium is a common clinical problem in hospitalized older patients that is associated with prolonged hospitalization, functional and cognitive decline, institutionalization, death, and increased health care costs.5 Despite a potential benefit of SPV CDS intervention in reducing vital sign checks and increasing sleep opportunity, this intervention did not reduce the incidence of delirium in hospitalized patients. This finding is not surprising given that delirium has a multifactorial etiology (eg, metabolic derangements, infections, medication side effects and drug toxicity, hospital environment). A small modification in nighttime vital sign checks and sleep opportunity may have limited impact on optimizing sleep quality and does not address other risk factors for delirium. As such, a multicomponent nonpharmacologic approach that includes sleep enhancement, early mobilization, feeding assistance, fluid repletion, infection prevention, and other interventions should guide delirium prevention in the hospital setting. The SPV CDS intervention may play a role in the delivery of a multifaceted, nonpharmacologic delirium prevention intervention in high-risk individuals.
Sleep disruption is one of the multiple hazards of hospitalization frequently experience by hospitalized older patients. Other hazards, or hospital-associated stressors, include mobility restriction (eg, physical restraints such as urinary catheters and intravenous lines, bed elevation and rails), malnourishment and dehydration (eg, frequent use of no-food-by-mouth order, lack of easy access to hydration), and pain (eg, poor pain control). Extended exposures to these stressors may lead to a maladaptive state called allostatic overload that transiently increases vulnerability to post-hospitalization adverse events, including emergency department use, hospital readmission, or death (ie, post-hospital syndrome).6 Thus, the optimization of sleep during hospitalization in vulnerable patients may have benefits that extend beyond delirium prevention. It is perceivable that a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, may be applied to reduce some of these hazards of hospitalization in addition to improving sleep opportunity.
Applications for Clinical Practice
Findings from the current study indicate that a CDS tool embedded in EHR that utilizes a real-time prediction algorithm of patient data may help to safely improve sleep opportunity in hospitalized patients. The participants in the current study were relatively young (53 [15] years). Given that age is a risk factor for delirium, the effects of this intervention on delirium prevention in the most susceptible population (ie, those over the age of 65) remain unknown and further investigation is warranted. Additional studies are needed to determine whether this approach yields similar results in geriatric patients and improves clinical outcomes.
—Fred Ko, MD
1. Institute of Medicine (US) Committee on Sleep Medicine and Research. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Colten HR, Altevogt BM, editors. National Academies Press (US); 2006.
2. Pilkington S. Causes and consequences of sleep deprivation in hospitalised patients. Nurs Stand. 2013;27(49):350-342. doi:10.7748/ns2013.08.27.49.35.e7649
3. Stewart NH, Arora VM. Sleep in hospitalized older adults. Sleep Med Clin. 2018;13(1):127-135. doi:10.1016/j.jsmc.2017.09.012
4. Altman MT, Knauert MP, Pisani MA. Sleep disturbance after hospitalization and critical illness: a systematic review. Ann Am Thorac Soc. 2017;14(9):1457-1468. doi:10.1513/AnnalsATS.201702-148SR
5. Oh ES, Fong TG, Hshieh TT, Inouye SK. Delirium in older persons: advances in diagnosis and treatment. JAMA. 2017;318(12):1161-1174. doi:10.1001/jama.2017.12067
6. Goldwater DS, Dharmarajan K, McEwan BS, Krumholz HM. Is posthospital syndrome a result of hospitalization-induced allostatic overload? J Hosp Med. 2018;13(5). doi:10.12788/jhm.2986
1. Institute of Medicine (US) Committee on Sleep Medicine and Research. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Colten HR, Altevogt BM, editors. National Academies Press (US); 2006.
2. Pilkington S. Causes and consequences of sleep deprivation in hospitalised patients. Nurs Stand. 2013;27(49):350-342. doi:10.7748/ns2013.08.27.49.35.e7649
3. Stewart NH, Arora VM. Sleep in hospitalized older adults. Sleep Med Clin. 2018;13(1):127-135. doi:10.1016/j.jsmc.2017.09.012
4. Altman MT, Knauert MP, Pisani MA. Sleep disturbance after hospitalization and critical illness: a systematic review. Ann Am Thorac Soc. 2017;14(9):1457-1468. doi:10.1513/AnnalsATS.201702-148SR
5. Oh ES, Fong TG, Hshieh TT, Inouye SK. Delirium in older persons: advances in diagnosis and treatment. JAMA. 2017;318(12):1161-1174. doi:10.1001/jama.2017.12067
6. Goldwater DS, Dharmarajan K, McEwan BS, Krumholz HM. Is posthospital syndrome a result of hospitalization-induced allostatic overload? J Hosp Med. 2018;13(5). doi:10.12788/jhm.2986
Doctors treat osteoporosis with hormone therapy against guidelines
This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.
According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.
Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
Women’s Health Initiative findings
The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.
The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.
Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.
“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
Hormone therapy’s complex history
HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.
While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.
Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.
“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”
Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.
It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
Today’s use of HT in women with osteoporosis
Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.
“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.
“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.
“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.
Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.
“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.
According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.
“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
Additional scenarios when doctors may advise HT
“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.
“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”
Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.
“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”
“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.
“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”
Dr. Roberts added that HT would be more of a niche drug.
“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”
Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other experts interviewed for this piece reported no conflicts.
This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.
According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.
Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
Women’s Health Initiative findings
The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.
The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.
Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.
“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
Hormone therapy’s complex history
HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.
While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.
Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.
“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”
Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.
It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
Today’s use of HT in women with osteoporosis
Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.
“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.
“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.
“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.
Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.
“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.
According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.
“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
Additional scenarios when doctors may advise HT
“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.
“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”
Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.
“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”
“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.
“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”
Dr. Roberts added that HT would be more of a niche drug.
“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”
Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other experts interviewed for this piece reported no conflicts.
This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.
According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.
Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
Women’s Health Initiative findings
The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.
The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.
Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.
“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
Hormone therapy’s complex history
HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.
While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.
Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.
“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”
Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.
It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
Today’s use of HT in women with osteoporosis
Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.
“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.
“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.
“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.
Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.
“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.
According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.
“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
Additional scenarios when doctors may advise HT
“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.
“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”
Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.
“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”
“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.
“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”
Dr. Roberts added that HT would be more of a niche drug.
“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”
Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other experts interviewed for this piece reported no conflicts.
Ways to lessen toxic effects of chemo in older adults
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Restoring ‘sixth sense’ may reduce falls in Alzheimer’s
(AD), new research confirms.
Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.
However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.
The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.
“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”
The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
The ‘sixth hidden sense’
The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.
“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”
Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.
The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.
Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.
Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.
To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.
“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.
Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
Can therapy help?
Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.
“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.
Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.
While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.
“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.
“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”
Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.
Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.
The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AD), new research confirms.
Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.
However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.
The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.
“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”
The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
The ‘sixth hidden sense’
The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.
“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”
Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.
The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.
Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.
Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.
To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.
“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.
Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
Can therapy help?
Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.
“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.
Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.
While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.
“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.
“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”
Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.
Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.
The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AD), new research confirms.
Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.
However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.
The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.
“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”
The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
The ‘sixth hidden sense’
The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.
“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”
Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.
The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.
Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.
Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.
To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.
“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.
Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
Can therapy help?
Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.
“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.
Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.
While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.
“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.
“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”
Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.
Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.
The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
FDA clears once-weekly transdermal patch for Alzheimer’s
Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.
Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.
“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.
“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.
The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.
The company expects the donepezil transdermal patch to be available in early Fall 2022.
A version of this article first appeared on Medscape.com.
Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.
Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.
“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.
“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.
The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.
The company expects the donepezil transdermal patch to be available in early Fall 2022.
A version of this article first appeared on Medscape.com.
Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.
Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.
“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.
“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.
The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.
The company expects the donepezil transdermal patch to be available in early Fall 2022.
A version of this article first appeared on Medscape.com.
Handheld ECGs ease AFib screening in the very elderly
The use of handheld, single-lead electrocardiograms (ECGs) did not increase diagnoses of AFib overall in patients aged 65 and older, but it did in patients 85 and up, researchers reported in Circulation.
“Incorporating single-lead ECGs into routine medical assessments as a new vital sign was widely feasible. Over 90% of people who were offered screening agreed to it and underwent screening,” said Steven Lubitz, MD, of the Cardiac Arrhythmia Service and Cardiovascular Research Center at Massachusetts General Hospital, Boston, who led the study.
Because advanced age is associated with a substantially increased risk of both AFib and stroke, point-of-care screening might be an efficient use of handheld ECGs, Dr. Lubitz said.
“The technology simply requires patients to place their fingers on the device to record an electrocardiogram and can be easily embedded in the routine clinical practice of primary care physicians,” he said in an interview.
The typical person has a 30% lifetime risk of developing AFib, and the chances of experiencing a stroke associated with the arrhythmia can be reduced significantly with anticoagulants, Dr. Lubitz said.
Professional organizations are split about the utility of screening for AFib. The European Society of Cardiology recommends opportunistic screening with either pulse palpation or ECG rhythm strip at clinic visits for patients 65 and older. The National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand have issued similar guidelines.
However, screening for AFib is not considered standard of care in the United States – although Dr. Lubitz predicted that that would change.
“I think the guidelines in the United States will evolve in the next few years, because I think we’re getting closer to understanding who we should be screening for atrial fibrillation and how we should be screening,” Dr. Lubitz told this news organization.
‘Very reassuring’ results
The randomized controlled trial found that for patients 85 and older, use of handheld ECGs led to a nearly 2% increase in new diagnoses of AFib in the screening group compared to conventional care.
The researchers also demonstrated an increased likelihood of diagnosing AFib during the patient’s primary-care encounter than at other sites, such as the emergency department or inpatient settings that might be more costly and resource-intensive. Moreover, the study reported that point-of-care screening was associated with high rates of oral anticoagulation prescriptions written for patients with newly diagnosed AFib, a finding Dr. Lubitz called “very reassuring.”
The Mass General researchers used single-lead devices attached to a tablet computer to screen more than 35,000 men and women from 16 primary care sites affiliated with the hospital’s practice-based research network.
Half the sites were randomly selected to include the screening intervention, where medical assistants used handheld ECGs at the start of the visit while checking routine vital signs.
The 1-year study screened 91% of eligible patients, demonstrating that single-lead rhythm assessment is feasible as part of routine primary care practice, Dr. Lubitz said. This finding supports other studies suggesting that handheld devices can enable rapid and scalable mass screening.
“We demonstrated that integration into routine practice by clinical personnel – in this case, medical assistants – is feasible. No study has measured and demonstrated such a high integration with routine care, reflecting both patient interest in screening and feasibility of incorporating screening into busy clinical practices,” Dr. Lubitz said.
Mobile ECGs with the handheld device take about 30 seconds to perform. In contrast, standard ECGs used in outpatient practices are bulky, and recording the ECG can take roughly 10 minutes.
Anthony Leazzo, DO, chairman of family practice at Northwestern Medicine Delnor Hospital, in Geneva, Ill., noted that smartwatches provide an alternative technology for detecting AFib.
But “a handheld, one-lead device would be more beneficial and should be more sensitive by measuring electrical activity similar to a normal ECG,” he said.
However, Dr. Leazzo said using such technology would need to be cost-effective because the patients at highest risk for AFib usually are on fixed incomes. Consumer versions of the devices can cost under $100. Dr. Lubitz said the actual cost for devices and a software platform used for a medical enterprise may differ.
Handheld ECGs are gradually being integrated into clinical practices, a trend driven by the rapid growth of telemedicine to remotely assess patients, Dr. Lubitz said.
“Our work affirmed that single-lead devices generate information for the physician that is actionable, though the proportion of newly detected AFib cases using a point-of-care ECG screening approach is likely to be very small,” Dr. Lubitz said in an interview. “For that reason, we think handheld devices are best deployed for people at the highest risk of AFib and stroke, and age is an excellent surrogate for that determination.”
The study was funded by Bristol-Myers Squibb–Pfizer Alliance.
A version of this article first appeared on Medscape.com.
The use of handheld, single-lead electrocardiograms (ECGs) did not increase diagnoses of AFib overall in patients aged 65 and older, but it did in patients 85 and up, researchers reported in Circulation.
“Incorporating single-lead ECGs into routine medical assessments as a new vital sign was widely feasible. Over 90% of people who were offered screening agreed to it and underwent screening,” said Steven Lubitz, MD, of the Cardiac Arrhythmia Service and Cardiovascular Research Center at Massachusetts General Hospital, Boston, who led the study.
Because advanced age is associated with a substantially increased risk of both AFib and stroke, point-of-care screening might be an efficient use of handheld ECGs, Dr. Lubitz said.
“The technology simply requires patients to place their fingers on the device to record an electrocardiogram and can be easily embedded in the routine clinical practice of primary care physicians,” he said in an interview.
The typical person has a 30% lifetime risk of developing AFib, and the chances of experiencing a stroke associated with the arrhythmia can be reduced significantly with anticoagulants, Dr. Lubitz said.
Professional organizations are split about the utility of screening for AFib. The European Society of Cardiology recommends opportunistic screening with either pulse palpation or ECG rhythm strip at clinic visits for patients 65 and older. The National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand have issued similar guidelines.
However, screening for AFib is not considered standard of care in the United States – although Dr. Lubitz predicted that that would change.
“I think the guidelines in the United States will evolve in the next few years, because I think we’re getting closer to understanding who we should be screening for atrial fibrillation and how we should be screening,” Dr. Lubitz told this news organization.
‘Very reassuring’ results
The randomized controlled trial found that for patients 85 and older, use of handheld ECGs led to a nearly 2% increase in new diagnoses of AFib in the screening group compared to conventional care.
The researchers also demonstrated an increased likelihood of diagnosing AFib during the patient’s primary-care encounter than at other sites, such as the emergency department or inpatient settings that might be more costly and resource-intensive. Moreover, the study reported that point-of-care screening was associated with high rates of oral anticoagulation prescriptions written for patients with newly diagnosed AFib, a finding Dr. Lubitz called “very reassuring.”
The Mass General researchers used single-lead devices attached to a tablet computer to screen more than 35,000 men and women from 16 primary care sites affiliated with the hospital’s practice-based research network.
Half the sites were randomly selected to include the screening intervention, where medical assistants used handheld ECGs at the start of the visit while checking routine vital signs.
The 1-year study screened 91% of eligible patients, demonstrating that single-lead rhythm assessment is feasible as part of routine primary care practice, Dr. Lubitz said. This finding supports other studies suggesting that handheld devices can enable rapid and scalable mass screening.
“We demonstrated that integration into routine practice by clinical personnel – in this case, medical assistants – is feasible. No study has measured and demonstrated such a high integration with routine care, reflecting both patient interest in screening and feasibility of incorporating screening into busy clinical practices,” Dr. Lubitz said.
Mobile ECGs with the handheld device take about 30 seconds to perform. In contrast, standard ECGs used in outpatient practices are bulky, and recording the ECG can take roughly 10 minutes.
Anthony Leazzo, DO, chairman of family practice at Northwestern Medicine Delnor Hospital, in Geneva, Ill., noted that smartwatches provide an alternative technology for detecting AFib.
But “a handheld, one-lead device would be more beneficial and should be more sensitive by measuring electrical activity similar to a normal ECG,” he said.
However, Dr. Leazzo said using such technology would need to be cost-effective because the patients at highest risk for AFib usually are on fixed incomes. Consumer versions of the devices can cost under $100. Dr. Lubitz said the actual cost for devices and a software platform used for a medical enterprise may differ.
Handheld ECGs are gradually being integrated into clinical practices, a trend driven by the rapid growth of telemedicine to remotely assess patients, Dr. Lubitz said.
“Our work affirmed that single-lead devices generate information for the physician that is actionable, though the proportion of newly detected AFib cases using a point-of-care ECG screening approach is likely to be very small,” Dr. Lubitz said in an interview. “For that reason, we think handheld devices are best deployed for people at the highest risk of AFib and stroke, and age is an excellent surrogate for that determination.”
The study was funded by Bristol-Myers Squibb–Pfizer Alliance.
A version of this article first appeared on Medscape.com.
The use of handheld, single-lead electrocardiograms (ECGs) did not increase diagnoses of AFib overall in patients aged 65 and older, but it did in patients 85 and up, researchers reported in Circulation.
“Incorporating single-lead ECGs into routine medical assessments as a new vital sign was widely feasible. Over 90% of people who were offered screening agreed to it and underwent screening,” said Steven Lubitz, MD, of the Cardiac Arrhythmia Service and Cardiovascular Research Center at Massachusetts General Hospital, Boston, who led the study.
Because advanced age is associated with a substantially increased risk of both AFib and stroke, point-of-care screening might be an efficient use of handheld ECGs, Dr. Lubitz said.
“The technology simply requires patients to place their fingers on the device to record an electrocardiogram and can be easily embedded in the routine clinical practice of primary care physicians,” he said in an interview.
The typical person has a 30% lifetime risk of developing AFib, and the chances of experiencing a stroke associated with the arrhythmia can be reduced significantly with anticoagulants, Dr. Lubitz said.
Professional organizations are split about the utility of screening for AFib. The European Society of Cardiology recommends opportunistic screening with either pulse palpation or ECG rhythm strip at clinic visits for patients 65 and older. The National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand have issued similar guidelines.
However, screening for AFib is not considered standard of care in the United States – although Dr. Lubitz predicted that that would change.
“I think the guidelines in the United States will evolve in the next few years, because I think we’re getting closer to understanding who we should be screening for atrial fibrillation and how we should be screening,” Dr. Lubitz told this news organization.
‘Very reassuring’ results
The randomized controlled trial found that for patients 85 and older, use of handheld ECGs led to a nearly 2% increase in new diagnoses of AFib in the screening group compared to conventional care.
The researchers also demonstrated an increased likelihood of diagnosing AFib during the patient’s primary-care encounter than at other sites, such as the emergency department or inpatient settings that might be more costly and resource-intensive. Moreover, the study reported that point-of-care screening was associated with high rates of oral anticoagulation prescriptions written for patients with newly diagnosed AFib, a finding Dr. Lubitz called “very reassuring.”
The Mass General researchers used single-lead devices attached to a tablet computer to screen more than 35,000 men and women from 16 primary care sites affiliated with the hospital’s practice-based research network.
Half the sites were randomly selected to include the screening intervention, where medical assistants used handheld ECGs at the start of the visit while checking routine vital signs.
The 1-year study screened 91% of eligible patients, demonstrating that single-lead rhythm assessment is feasible as part of routine primary care practice, Dr. Lubitz said. This finding supports other studies suggesting that handheld devices can enable rapid and scalable mass screening.
“We demonstrated that integration into routine practice by clinical personnel – in this case, medical assistants – is feasible. No study has measured and demonstrated such a high integration with routine care, reflecting both patient interest in screening and feasibility of incorporating screening into busy clinical practices,” Dr. Lubitz said.
Mobile ECGs with the handheld device take about 30 seconds to perform. In contrast, standard ECGs used in outpatient practices are bulky, and recording the ECG can take roughly 10 minutes.
Anthony Leazzo, DO, chairman of family practice at Northwestern Medicine Delnor Hospital, in Geneva, Ill., noted that smartwatches provide an alternative technology for detecting AFib.
But “a handheld, one-lead device would be more beneficial and should be more sensitive by measuring electrical activity similar to a normal ECG,” he said.
However, Dr. Leazzo said using such technology would need to be cost-effective because the patients at highest risk for AFib usually are on fixed incomes. Consumer versions of the devices can cost under $100. Dr. Lubitz said the actual cost for devices and a software platform used for a medical enterprise may differ.
Handheld ECGs are gradually being integrated into clinical practices, a trend driven by the rapid growth of telemedicine to remotely assess patients, Dr. Lubitz said.
“Our work affirmed that single-lead devices generate information for the physician that is actionable, though the proportion of newly detected AFib cases using a point-of-care ECG screening approach is likely to be very small,” Dr. Lubitz said in an interview. “For that reason, we think handheld devices are best deployed for people at the highest risk of AFib and stroke, and age is an excellent surrogate for that determination.”
The study was funded by Bristol-Myers Squibb–Pfizer Alliance.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Tremors and memory loss precede Parkinson’s in diverse population
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
FROM JAMA NEUROLOGY
Boosting daily exercise after age 70 tied to lower CVD risk
Increasingly active patterns of physical activity were linked with reduced rates of overall mortality and cardiovascular disease (CVD), but early rather than later in late life, in a 20-year follow-up cohort study.
In this population of people older than 65 years, researchers found that physical activity overall was associated with lower rates of incident CVD, particularly among men, and the association was strongest in people 70 to 75 years of age, rather than in older age groups.
They also looked at “trajectories,” or changes in activity over time, and found that a stable-high trajectory of activity was associated with a significantly lower risk for cardiovascular outcomes in men than in those with a stable-low trajectory. For women, more physical activity was consistently associated with lower CVD outcomes, although not statistically significantly so, except for overall mortality, which did reach significance.
Notably, the greatest reduction in cardiovascular risk was reported in people who did more than 20 minutes of physical exercise each day, and it was more pronounced in those 70 years of age.
Physical activity was also associated with a lower incidence of heart failure and coronary heart disease in older people, again especially early on in late life, reported Claudio Barbiellini Amidei, MD, University of Padua, Italy, and colleagues.
The data suggest that physical activity is more effective in preventing CVD onset when implemented early rather than later in life, noted Dr. Amidei in an email.
“The findings of our study are suggestive of a protective effect of physical activity in late-life on cardiovascular health. WHO recommendations for adults and older adults are to practice at least 20 minutes of moderate to vigorous physical activity per day. I believe this is a realistic target, and policy makers should raise awareness on the importance of achieving this goal at all ages, including in late-life,” Dr. Amidei said.
The study was published online Feb. 14 in Heart.
Previous research has demonstrated that the most benefit of high physical activity, compared with low, begins at about 60 years of age, and that is because younger people are at much lower risk, noted Carl “Chip” Lavie MD, FACC, medical director of cardiac rehabilitation and prevention, Ochsner Clinical School–The University of Queensland School of Medicine, New Orleans, who was not involved in the study.
“At quite old ages, for example over age 80, resistance exercise or weight training and balance training may be even more important than aerobic training,” he added.
Activity ‘trajectories’
The benefits of physical activity on cardiovascular risk are well established, the researchers note. Less clear is the role that trajectories of activity over time play, although research to date suggests a reduction in risk with increasing activity from mid-life to early old age, they write.
For the current analysis, the researchers assessed 3,099 Italian participants. Mean age was about 75 years, and baseline data were collected from 1995 to 1997.
Follow-up visits were conducted after 4 years and again after 7 years. Using hospital medical records and mortality data, the researchers were able to collect surveillance data through 2018. Hospital records, surveys, and clinical assessments helped them identify incident and prevalent cardiovascular diseases, such as stroke, coronary heart disease, and heart failure.
Participants’ physical activity patterns were classified as stable-high, low-increasing, high-decreasing, and stable-low. Exposure was evaluated at 70, 75, 80, and 85 years of age.
“In our analyses, we focused on moderate to vigorous physical activity, and these include a broad range of exercises, such as walking very briskly, playing tennis, [and] jogging, but comprise also other activities, such as gardening or doing household chores,” said Dr. Amidei.
Patterns of stable-low physical activity were linked to a significantly greater risk for cardiovascular outcomes in men than patterns of stable-high physical activity (hazard ratio, 0.48; 95% confidence interval, 0.27-0.86; P for trend = .002).
No significant relation was found between physical activity and stroke, the researchers note.
“The benefits of physical activity seem to lessen above the age of 75 years and seem more important in men,” noted Dr. Lavie. “This may be partly due to the higher risk of CVD in men. Women typically lag 13 to 15 years behind men for CVD but start catching up in older years.”
Limitations of the study include lack of information regarding physical activity during mid-life, the limited number of stroke events, the relatively few participants older than 85 years, and potential recall bias, the researchers note.
Another limitation was that the physical activity data were based on patient surveys collected 3 years apart and did not involve the use of an accelerometer, the researchers add.
“Future observational studies are required to confirm our findings and pathophysiological studies are warranted to examine the underlying biological mechanisms. Physical activity is likely to be beneficial at any age, but to summarize our findings, we could say that when it comes to being physically active, the sooner the better,” concluded Dr. Amidei.
Dr. Amidei reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Increasingly active patterns of physical activity were linked with reduced rates of overall mortality and cardiovascular disease (CVD), but early rather than later in late life, in a 20-year follow-up cohort study.
In this population of people older than 65 years, researchers found that physical activity overall was associated with lower rates of incident CVD, particularly among men, and the association was strongest in people 70 to 75 years of age, rather than in older age groups.
They also looked at “trajectories,” or changes in activity over time, and found that a stable-high trajectory of activity was associated with a significantly lower risk for cardiovascular outcomes in men than in those with a stable-low trajectory. For women, more physical activity was consistently associated with lower CVD outcomes, although not statistically significantly so, except for overall mortality, which did reach significance.
Notably, the greatest reduction in cardiovascular risk was reported in people who did more than 20 minutes of physical exercise each day, and it was more pronounced in those 70 years of age.
Physical activity was also associated with a lower incidence of heart failure and coronary heart disease in older people, again especially early on in late life, reported Claudio Barbiellini Amidei, MD, University of Padua, Italy, and colleagues.
The data suggest that physical activity is more effective in preventing CVD onset when implemented early rather than later in life, noted Dr. Amidei in an email.
“The findings of our study are suggestive of a protective effect of physical activity in late-life on cardiovascular health. WHO recommendations for adults and older adults are to practice at least 20 minutes of moderate to vigorous physical activity per day. I believe this is a realistic target, and policy makers should raise awareness on the importance of achieving this goal at all ages, including in late-life,” Dr. Amidei said.
The study was published online Feb. 14 in Heart.
Previous research has demonstrated that the most benefit of high physical activity, compared with low, begins at about 60 years of age, and that is because younger people are at much lower risk, noted Carl “Chip” Lavie MD, FACC, medical director of cardiac rehabilitation and prevention, Ochsner Clinical School–The University of Queensland School of Medicine, New Orleans, who was not involved in the study.
“At quite old ages, for example over age 80, resistance exercise or weight training and balance training may be even more important than aerobic training,” he added.
Activity ‘trajectories’
The benefits of physical activity on cardiovascular risk are well established, the researchers note. Less clear is the role that trajectories of activity over time play, although research to date suggests a reduction in risk with increasing activity from mid-life to early old age, they write.
For the current analysis, the researchers assessed 3,099 Italian participants. Mean age was about 75 years, and baseline data were collected from 1995 to 1997.
Follow-up visits were conducted after 4 years and again after 7 years. Using hospital medical records and mortality data, the researchers were able to collect surveillance data through 2018. Hospital records, surveys, and clinical assessments helped them identify incident and prevalent cardiovascular diseases, such as stroke, coronary heart disease, and heart failure.
Participants’ physical activity patterns were classified as stable-high, low-increasing, high-decreasing, and stable-low. Exposure was evaluated at 70, 75, 80, and 85 years of age.
“In our analyses, we focused on moderate to vigorous physical activity, and these include a broad range of exercises, such as walking very briskly, playing tennis, [and] jogging, but comprise also other activities, such as gardening or doing household chores,” said Dr. Amidei.
Patterns of stable-low physical activity were linked to a significantly greater risk for cardiovascular outcomes in men than patterns of stable-high physical activity (hazard ratio, 0.48; 95% confidence interval, 0.27-0.86; P for trend = .002).
No significant relation was found between physical activity and stroke, the researchers note.
“The benefits of physical activity seem to lessen above the age of 75 years and seem more important in men,” noted Dr. Lavie. “This may be partly due to the higher risk of CVD in men. Women typically lag 13 to 15 years behind men for CVD but start catching up in older years.”
Limitations of the study include lack of information regarding physical activity during mid-life, the limited number of stroke events, the relatively few participants older than 85 years, and potential recall bias, the researchers note.
Another limitation was that the physical activity data were based on patient surveys collected 3 years apart and did not involve the use of an accelerometer, the researchers add.
“Future observational studies are required to confirm our findings and pathophysiological studies are warranted to examine the underlying biological mechanisms. Physical activity is likely to be beneficial at any age, but to summarize our findings, we could say that when it comes to being physically active, the sooner the better,” concluded Dr. Amidei.
Dr. Amidei reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Increasingly active patterns of physical activity were linked with reduced rates of overall mortality and cardiovascular disease (CVD), but early rather than later in late life, in a 20-year follow-up cohort study.
In this population of people older than 65 years, researchers found that physical activity overall was associated with lower rates of incident CVD, particularly among men, and the association was strongest in people 70 to 75 years of age, rather than in older age groups.
They also looked at “trajectories,” or changes in activity over time, and found that a stable-high trajectory of activity was associated with a significantly lower risk for cardiovascular outcomes in men than in those with a stable-low trajectory. For women, more physical activity was consistently associated with lower CVD outcomes, although not statistically significantly so, except for overall mortality, which did reach significance.
Notably, the greatest reduction in cardiovascular risk was reported in people who did more than 20 minutes of physical exercise each day, and it was more pronounced in those 70 years of age.
Physical activity was also associated with a lower incidence of heart failure and coronary heart disease in older people, again especially early on in late life, reported Claudio Barbiellini Amidei, MD, University of Padua, Italy, and colleagues.
The data suggest that physical activity is more effective in preventing CVD onset when implemented early rather than later in life, noted Dr. Amidei in an email.
“The findings of our study are suggestive of a protective effect of physical activity in late-life on cardiovascular health. WHO recommendations for adults and older adults are to practice at least 20 minutes of moderate to vigorous physical activity per day. I believe this is a realistic target, and policy makers should raise awareness on the importance of achieving this goal at all ages, including in late-life,” Dr. Amidei said.
The study was published online Feb. 14 in Heart.
Previous research has demonstrated that the most benefit of high physical activity, compared with low, begins at about 60 years of age, and that is because younger people are at much lower risk, noted Carl “Chip” Lavie MD, FACC, medical director of cardiac rehabilitation and prevention, Ochsner Clinical School–The University of Queensland School of Medicine, New Orleans, who was not involved in the study.
“At quite old ages, for example over age 80, resistance exercise or weight training and balance training may be even more important than aerobic training,” he added.
Activity ‘trajectories’
The benefits of physical activity on cardiovascular risk are well established, the researchers note. Less clear is the role that trajectories of activity over time play, although research to date suggests a reduction in risk with increasing activity from mid-life to early old age, they write.
For the current analysis, the researchers assessed 3,099 Italian participants. Mean age was about 75 years, and baseline data were collected from 1995 to 1997.
Follow-up visits were conducted after 4 years and again after 7 years. Using hospital medical records and mortality data, the researchers were able to collect surveillance data through 2018. Hospital records, surveys, and clinical assessments helped them identify incident and prevalent cardiovascular diseases, such as stroke, coronary heart disease, and heart failure.
Participants’ physical activity patterns were classified as stable-high, low-increasing, high-decreasing, and stable-low. Exposure was evaluated at 70, 75, 80, and 85 years of age.
“In our analyses, we focused on moderate to vigorous physical activity, and these include a broad range of exercises, such as walking very briskly, playing tennis, [and] jogging, but comprise also other activities, such as gardening or doing household chores,” said Dr. Amidei.
Patterns of stable-low physical activity were linked to a significantly greater risk for cardiovascular outcomes in men than patterns of stable-high physical activity (hazard ratio, 0.48; 95% confidence interval, 0.27-0.86; P for trend = .002).
No significant relation was found between physical activity and stroke, the researchers note.
“The benefits of physical activity seem to lessen above the age of 75 years and seem more important in men,” noted Dr. Lavie. “This may be partly due to the higher risk of CVD in men. Women typically lag 13 to 15 years behind men for CVD but start catching up in older years.”
Limitations of the study include lack of information regarding physical activity during mid-life, the limited number of stroke events, the relatively few participants older than 85 years, and potential recall bias, the researchers note.
Another limitation was that the physical activity data were based on patient surveys collected 3 years apart and did not involve the use of an accelerometer, the researchers add.
“Future observational studies are required to confirm our findings and pathophysiological studies are warranted to examine the underlying biological mechanisms. Physical activity is likely to be beneficial at any age, but to summarize our findings, we could say that when it comes to being physically active, the sooner the better,” concluded Dr. Amidei.
Dr. Amidei reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.