Geriatrics

Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.

Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.

The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.

“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York. 

“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.

The study was published online in JAMA Network Open.
 

Off-Label Prescribing Common

The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.

The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.

While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.

The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.

In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.

The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation. 

The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
 

Low-Cost, Effective Intervention

While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.

PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).

The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).

Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.

Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.

Results were similar for patients living in the community.

Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).

The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.

Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.

The authors received support from the National Institute on Aging. They reported no relevant financial relationships.

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

Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.

Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.

The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.

“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York. 

“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.

The study was published online in JAMA Network Open.
 

Off-Label Prescribing Common

The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.

The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.

While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.

The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.

In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.

The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation. 

The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
 

Low-Cost, Effective Intervention

While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.

PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).

The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).

Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.

Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.

Results were similar for patients living in the community.

Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).

The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.

Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.

The authors received support from the National Institute on Aging. They reported no relevant financial relationships.

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

Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.

Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.

The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.

“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York. 

“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.

The study was published online in JAMA Network Open.
 

Off-Label Prescribing Common

The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.

The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.

While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.

The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.

In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.

The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation. 

The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
 

Low-Cost, Effective Intervention

While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.

PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).

The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).

Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.

Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.

Results were similar for patients living in the community.

Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).

The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.

Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.

The authors received support from the National Institute on Aging. They reported no relevant financial relationships.

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

Racial discrimination in Black Americans is associated with an increased risk of developing Alzheimer’s disease (AD) in later life, new findings showed.

Researchers found that Black Americans who experience racism in their 40s and 50s are more likely to have increased serum levels of AD biomarkers p-tau181 and neurofilament light (NfL) more than a decade later.

“We know that Black Americans are at an elevated risk of Alzheimer’s disease and other dementias compared to non-Hispanic White Americans, but we don’t fully understand all the factors that contribute to this disproportionate risk,” Michelle Mielke, PhD, co-author and professor of epidemiology and prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in a press release.

Recent data show AD is twice as prevalent in Black Americans as in Whites, at 18.6% and 10%, respectively. Dr. Mielke said this level of disparity cannot be attributed solely to genetic differences, and evidence suggests that racism and its related stress may play a role.

The findings were published online in Alzheimer’s and Dementia.
 

AD Biomarker Testing

To further explore a possible link between exposure to racism and AD risk, investigators analyzed data from the Family and Community Health Study, a multisite, longitudinal investigation that included more than 800 families in the United States.

Blood samples and information on racial discrimination were collected from 255 middle-aged Black Americans between 2002 and 2005.

Blood samples were tested for serum phosphorylated tau181 (p-Tau181), a marker of AD pathology; NfL, a nonspecific marker of neurodegeneration; and glial fibrillary acidic protein (GFAP), a marker of brain inflammation.

Participants answered questions about racial discrimination, which included whether they have been subjected to disrespectful treatment including racial slurs, harassment from law enforcement, or if they had ever been excluded from social activities because of their race.

The sample included 212 females and 43 males with a mean age of 46. Most participants (70%) lived in urban areas.
 

Stress-Related?

Investigators found no correlation between racial discrimination and increased levels of AD blood biomarkers in 2008 when participants were a mean age of 46 years. However, 11 years later, when participants were roughly 57 years old, investigators found experiencing racism in middle age was significantly correlated with higher levels of both p-Tau181 (r = 0.158; P ≤ .012) and NfL (r = 0.143; P ≤ .023). There was no significant association between reported discrimination and GFAP.

“These findings support the hypothesis that unique life stressors encountered by Black Americans in midlife become biologically embedded and contribute to AD pathology and neurodegeneration later in life,” the authors wrote.

Investigators speculated based on previous research that the stress related to discrimination may be associated with reductions in hippocampal and prefrontal cortex volumes and neurodegeneration in general.

Dr. Mielke also said it’s clear that future studies should focus on racism experienced by Black Americans to further understand their risk for dementia.

“This research can help inform policies and interventions to reduce racial disparities and reduce dementia risk,” she said.

Study limitations include the absence of amyloid biomarkers. Investigators noted that participants had non-detectable levels of amyloid, likely due to the use of serum vs cerebrospinal fluid.

The study was funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute. Mielke reported serving on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio.

A version of this article appeared on Medscape.com.

Racial discrimination in Black Americans is associated with an increased risk of developing Alzheimer’s disease (AD) in later life, new findings showed.

Researchers found that Black Americans who experience racism in their 40s and 50s are more likely to have increased serum levels of AD biomarkers p-tau181 and neurofilament light (NfL) more than a decade later.

“We know that Black Americans are at an elevated risk of Alzheimer’s disease and other dementias compared to non-Hispanic White Americans, but we don’t fully understand all the factors that contribute to this disproportionate risk,” Michelle Mielke, PhD, co-author and professor of epidemiology and prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in a press release.

Recent data show AD is twice as prevalent in Black Americans as in Whites, at 18.6% and 10%, respectively. Dr. Mielke said this level of disparity cannot be attributed solely to genetic differences, and evidence suggests that racism and its related stress may play a role.

The findings were published online in Alzheimer’s and Dementia.
 

AD Biomarker Testing

To further explore a possible link between exposure to racism and AD risk, investigators analyzed data from the Family and Community Health Study, a multisite, longitudinal investigation that included more than 800 families in the United States.

Blood samples and information on racial discrimination were collected from 255 middle-aged Black Americans between 2002 and 2005.

Blood samples were tested for serum phosphorylated tau181 (p-Tau181), a marker of AD pathology; NfL, a nonspecific marker of neurodegeneration; and glial fibrillary acidic protein (GFAP), a marker of brain inflammation.

Participants answered questions about racial discrimination, which included whether they have been subjected to disrespectful treatment including racial slurs, harassment from law enforcement, or if they had ever been excluded from social activities because of their race.

The sample included 212 females and 43 males with a mean age of 46. Most participants (70%) lived in urban areas.
 

Stress-Related?

Investigators found no correlation between racial discrimination and increased levels of AD blood biomarkers in 2008 when participants were a mean age of 46 years. However, 11 years later, when participants were roughly 57 years old, investigators found experiencing racism in middle age was significantly correlated with higher levels of both p-Tau181 (r = 0.158; P ≤ .012) and NfL (r = 0.143; P ≤ .023). There was no significant association between reported discrimination and GFAP.

“These findings support the hypothesis that unique life stressors encountered by Black Americans in midlife become biologically embedded and contribute to AD pathology and neurodegeneration later in life,” the authors wrote.

Investigators speculated based on previous research that the stress related to discrimination may be associated with reductions in hippocampal and prefrontal cortex volumes and neurodegeneration in general.

Dr. Mielke also said it’s clear that future studies should focus on racism experienced by Black Americans to further understand their risk for dementia.

“This research can help inform policies and interventions to reduce racial disparities and reduce dementia risk,” she said.

Study limitations include the absence of amyloid biomarkers. Investigators noted that participants had non-detectable levels of amyloid, likely due to the use of serum vs cerebrospinal fluid.

The study was funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute. Mielke reported serving on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio.

A version of this article appeared on Medscape.com.

Racial discrimination in Black Americans is associated with an increased risk of developing Alzheimer’s disease (AD) in later life, new findings showed.

Researchers found that Black Americans who experience racism in their 40s and 50s are more likely to have increased serum levels of AD biomarkers p-tau181 and neurofilament light (NfL) more than a decade later.

“We know that Black Americans are at an elevated risk of Alzheimer’s disease and other dementias compared to non-Hispanic White Americans, but we don’t fully understand all the factors that contribute to this disproportionate risk,” Michelle Mielke, PhD, co-author and professor of epidemiology and prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in a press release.

Recent data show AD is twice as prevalent in Black Americans as in Whites, at 18.6% and 10%, respectively. Dr. Mielke said this level of disparity cannot be attributed solely to genetic differences, and evidence suggests that racism and its related stress may play a role.

The findings were published online in Alzheimer’s and Dementia.
 

AD Biomarker Testing

To further explore a possible link between exposure to racism and AD risk, investigators analyzed data from the Family and Community Health Study, a multisite, longitudinal investigation that included more than 800 families in the United States.

Blood samples and information on racial discrimination were collected from 255 middle-aged Black Americans between 2002 and 2005.

Blood samples were tested for serum phosphorylated tau181 (p-Tau181), a marker of AD pathology; NfL, a nonspecific marker of neurodegeneration; and glial fibrillary acidic protein (GFAP), a marker of brain inflammation.

Participants answered questions about racial discrimination, which included whether they have been subjected to disrespectful treatment including racial slurs, harassment from law enforcement, or if they had ever been excluded from social activities because of their race.

The sample included 212 females and 43 males with a mean age of 46. Most participants (70%) lived in urban areas.
 

Stress-Related?

Investigators found no correlation between racial discrimination and increased levels of AD blood biomarkers in 2008 when participants were a mean age of 46 years. However, 11 years later, when participants were roughly 57 years old, investigators found experiencing racism in middle age was significantly correlated with higher levels of both p-Tau181 (r = 0.158; P ≤ .012) and NfL (r = 0.143; P ≤ .023). There was no significant association between reported discrimination and GFAP.

“These findings support the hypothesis that unique life stressors encountered by Black Americans in midlife become biologically embedded and contribute to AD pathology and neurodegeneration later in life,” the authors wrote.

Investigators speculated based on previous research that the stress related to discrimination may be associated with reductions in hippocampal and prefrontal cortex volumes and neurodegeneration in general.

Dr. Mielke also said it’s clear that future studies should focus on racism experienced by Black Americans to further understand their risk for dementia.

“This research can help inform policies and interventions to reduce racial disparities and reduce dementia risk,” she said.

Study limitations include the absence of amyloid biomarkers. Investigators noted that participants had non-detectable levels of amyloid, likely due to the use of serum vs cerebrospinal fluid.

The study was funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute. Mielke reported serving on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio.

A version of this article appeared on Medscape.com.

Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS). 

Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.

But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.

The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.

Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic. 

The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh. 

“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.

Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.

Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.

Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.

The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab. 

“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.

Neither speaker reported any financial conflicts of interest.

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

Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS). 

Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.

But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.

The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.

Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic. 

The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh. 

“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.

Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.

Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.

Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.

The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab. 

“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.

Neither speaker reported any financial conflicts of interest.

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

Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS). 

Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.

But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.

The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.

Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic. 

The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh. 

“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.

Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.

Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.

Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.

The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab. 

“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.

Neither speaker reported any financial conflicts of interest.

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

In a recent article in the American Journal of Obstetrics & Gynecology, Rebecca C. Thurston, PhD, and Pauline Maki, PhD, leading scientists in the area of menopause’s impact on brain function, presented data from their assessment of 248 late perimenopausal and postmenopausal women who reported hot flashes, also known as vasomotor symptoms (VMS).

Hot flashes are known to be associated with changes in brain white matter, carotid atherosclerosis, brain function, and memory. Dr. Thurston and colleagues objectively measured VMS over 24 hours, using skin conductance monitoring. Plasma concentrations of Alzheimer’s disease biomarkers, including the amyloid beta 42–to–amyloid beta 40 ratio, were assessed. The mean age of study participants was 59 years, and they experienced a mean of five objective VMS daily.

A key finding was that VMS, particularly those occurring during sleep, were associated with a significantly lower amyloid beta 42–to–beta 40 ratio. This finding suggests that nighttime VMS may be a marker of risk for Alzheimer’s disease.

Previous research has found that menopausal hormone therapy is associated with favorable changes in Alzheimer’s disease biomarkers. Likewise, large observational studies have shown a lower incidence of Alzheimer’s disease among women who initiate hormone therapy in their late perimenopausal or early postmenopausal years and continue such therapy long term.

The findings of this important study by Thurston and colleagues provide further evidence to support the tantalizing possibility that agents that reduce nighttime hot flashes (including hormone therapy) may lower the subsequent incidence of Alzheimer’s disease in high-risk women.
 

Dr. Kaunitz is a tenured professor and associate chair in the department of obstetrics and gynecology at the University of Florida College of Medicine–Jacksonville, and medical director and director of menopause and gynecologic ultrasound services at the University of Florida Southside Women’s Health, Jacksonville. He disclosed ties to Sumitomo Pharma America, Mithra, Viatris, Bayer, Merck, Mylan (Viatris), and UpToDate.

A version of this article appeared on Medscape.com.

In a recent article in the American Journal of Obstetrics & Gynecology, Rebecca C. Thurston, PhD, and Pauline Maki, PhD, leading scientists in the area of menopause’s impact on brain function, presented data from their assessment of 248 late perimenopausal and postmenopausal women who reported hot flashes, also known as vasomotor symptoms (VMS).

Hot flashes are known to be associated with changes in brain white matter, carotid atherosclerosis, brain function, and memory. Dr. Thurston and colleagues objectively measured VMS over 24 hours, using skin conductance monitoring. Plasma concentrations of Alzheimer’s disease biomarkers, including the amyloid beta 42–to–amyloid beta 40 ratio, were assessed. The mean age of study participants was 59 years, and they experienced a mean of five objective VMS daily.

A key finding was that VMS, particularly those occurring during sleep, were associated with a significantly lower amyloid beta 42–to–beta 40 ratio. This finding suggests that nighttime VMS may be a marker of risk for Alzheimer’s disease.

Previous research has found that menopausal hormone therapy is associated with favorable changes in Alzheimer’s disease biomarkers. Likewise, large observational studies have shown a lower incidence of Alzheimer’s disease among women who initiate hormone therapy in their late perimenopausal or early postmenopausal years and continue such therapy long term.

The findings of this important study by Thurston and colleagues provide further evidence to support the tantalizing possibility that agents that reduce nighttime hot flashes (including hormone therapy) may lower the subsequent incidence of Alzheimer’s disease in high-risk women.
 

Dr. Kaunitz is a tenured professor and associate chair in the department of obstetrics and gynecology at the University of Florida College of Medicine–Jacksonville, and medical director and director of menopause and gynecologic ultrasound services at the University of Florida Southside Women’s Health, Jacksonville. He disclosed ties to Sumitomo Pharma America, Mithra, Viatris, Bayer, Merck, Mylan (Viatris), and UpToDate.

A version of this article appeared on Medscape.com.

In a recent article in the American Journal of Obstetrics & Gynecology, Rebecca C. Thurston, PhD, and Pauline Maki, PhD, leading scientists in the area of menopause’s impact on brain function, presented data from their assessment of 248 late perimenopausal and postmenopausal women who reported hot flashes, also known as vasomotor symptoms (VMS).

Hot flashes are known to be associated with changes in brain white matter, carotid atherosclerosis, brain function, and memory. Dr. Thurston and colleagues objectively measured VMS over 24 hours, using skin conductance monitoring. Plasma concentrations of Alzheimer’s disease biomarkers, including the amyloid beta 42–to–amyloid beta 40 ratio, were assessed. The mean age of study participants was 59 years, and they experienced a mean of five objective VMS daily.

A key finding was that VMS, particularly those occurring during sleep, were associated with a significantly lower amyloid beta 42–to–beta 40 ratio. This finding suggests that nighttime VMS may be a marker of risk for Alzheimer’s disease.

Previous research has found that menopausal hormone therapy is associated with favorable changes in Alzheimer’s disease biomarkers. Likewise, large observational studies have shown a lower incidence of Alzheimer’s disease among women who initiate hormone therapy in their late perimenopausal or early postmenopausal years and continue such therapy long term.

The findings of this important study by Thurston and colleagues provide further evidence to support the tantalizing possibility that agents that reduce nighttime hot flashes (including hormone therapy) may lower the subsequent incidence of Alzheimer’s disease in high-risk women.
 

Dr. Kaunitz is a tenured professor and associate chair in the department of obstetrics and gynecology at the University of Florida College of Medicine–Jacksonville, and medical director and director of menopause and gynecologic ultrasound services at the University of Florida Southside Women’s Health, Jacksonville. He disclosed ties to Sumitomo Pharma America, Mithra, Viatris, Bayer, Merck, Mylan (Viatris), and UpToDate.

A version of this article appeared on Medscape.com.

Lower urinary tract symptoms were significantly associated with lower scores on measures of cognitive impairment in older adults, based on data from approximately 10,000 individuals.

“We know that lower urinary tract symptoms are very common in aging men and women;” however, older adults often underreport symptoms and avoid seeking treatment, Belinda Williams, MD, of the University of Alabama, Birmingham, said in a presentation at the annual meeting of the American Geriatrics Society.

“Evidence also shows us that the incidence of lower urinary tract symptoms (LUTS) is higher in patients with dementia,” she said. However, the association between cognitive impairment and LUTS has not been well studied, she said.

To address this knowledge gap, Dr. Williams and colleagues reviewed data from older adults with and without LUTS who were enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study including 30,239 Black or White adults aged 45 years and older who completed telephone or in-home assessments in 2003-2007 and in 2013-2017.

The study population included 6062 women and 4438 men who responded to questionnaires about LUTS and completed several cognitive tests via telephone in 2019-2010. The tests evaluated verbal fluency, executive function, and memory, and included the Six-Item Screener, Animal Naming, Letter F naming, and word list learning; lower scores indicated poorer cognitive performance.

Participants who met the criteria for LUTS were categorized as having mild, moderate, or severe symptoms.

The researchers controlled for age, race, education, income, and urban/rural setting in a multivariate analysis. The mean ages of the women and men were 69 years and 63 years, respectively; 41% and 32% were Black, 59% and 68% were White.

Overall, 70% of women and 62% of men reported LUTS; 6.2% and 8.2%, respectively, met criteria for cognitive impairment. The association between cognitive impairment and LUTS was statistically significant for all specific tests (P < .01), but not for the global cognitive domain tests.

Black men were more likely to report LUTS than White men, but LUTS reports were similar between Black and White women.

Moderate LUTS was the most common degree of severity for men and women (54% and 64%, respectively).

The most common symptom overall was pre-toilet leakage (urge urinary incontinence), reported by 94% of women and 91% of men. The next most common symptoms for men and women were nocturia and urgency.

“We found that, across the board, in all the cognitive tests, LUTS were associated with lower cognitive test scores,” Dr. Williams said in her presentation. Little differences were seen on the Six-Item Screener, she noted, but when they further analyzed the data using scores lower than 4 to indicate cognitive impairment, they found significant association with LUTS, she said.

The results showing that the presence of LUTS was consistently associated with lower cognitive test scores of verbal fluency, executive function, and memory, are applicable in clinical practice, Dr. Williams said in her presentation.

“Recognizing the subtle changes in cognition among older adults with LUTS may impact treatment decisions,” she said. “For example, we can encourage and advise our patients to be physically and cognitively active and to avoid anticholinergic medications.”

Next steps for research include analyzing longitudinal changes in cognition among participants with and without LUTS, said Dr. Williams.

During a question-and-answer session, Dr. Williams agreed with a comment that incorporating cognitive screening strategies in to LUTS clinical pathways might be helpful, such as conducting a baseline Montreal Cognitive Assessment Test (MoCA) in patients with LUTS. “Periodic repeat MoCAs thereafter can help assess decline in cognition,” she said.

The study was supported by the National Institutes of Neurological Disorders and Stroke and the National Institute on Aging. The researchers had no financial conflicts to disclose.

Lower urinary tract symptoms were significantly associated with lower scores on measures of cognitive impairment in older adults, based on data from approximately 10,000 individuals.

“We know that lower urinary tract symptoms are very common in aging men and women;” however, older adults often underreport symptoms and avoid seeking treatment, Belinda Williams, MD, of the University of Alabama, Birmingham, said in a presentation at the annual meeting of the American Geriatrics Society.

“Evidence also shows us that the incidence of lower urinary tract symptoms (LUTS) is higher in patients with dementia,” she said. However, the association between cognitive impairment and LUTS has not been well studied, she said.

To address this knowledge gap, Dr. Williams and colleagues reviewed data from older adults with and without LUTS who were enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study including 30,239 Black or White adults aged 45 years and older who completed telephone or in-home assessments in 2003-2007 and in 2013-2017.

The study population included 6062 women and 4438 men who responded to questionnaires about LUTS and completed several cognitive tests via telephone in 2019-2010. The tests evaluated verbal fluency, executive function, and memory, and included the Six-Item Screener, Animal Naming, Letter F naming, and word list learning; lower scores indicated poorer cognitive performance.

Participants who met the criteria for LUTS were categorized as having mild, moderate, or severe symptoms.

The researchers controlled for age, race, education, income, and urban/rural setting in a multivariate analysis. The mean ages of the women and men were 69 years and 63 years, respectively; 41% and 32% were Black, 59% and 68% were White.

Overall, 70% of women and 62% of men reported LUTS; 6.2% and 8.2%, respectively, met criteria for cognitive impairment. The association between cognitive impairment and LUTS was statistically significant for all specific tests (P < .01), but not for the global cognitive domain tests.

Black men were more likely to report LUTS than White men, but LUTS reports were similar between Black and White women.

Moderate LUTS was the most common degree of severity for men and women (54% and 64%, respectively).

The most common symptom overall was pre-toilet leakage (urge urinary incontinence), reported by 94% of women and 91% of men. The next most common symptoms for men and women were nocturia and urgency.

“We found that, across the board, in all the cognitive tests, LUTS were associated with lower cognitive test scores,” Dr. Williams said in her presentation. Little differences were seen on the Six-Item Screener, she noted, but when they further analyzed the data using scores lower than 4 to indicate cognitive impairment, they found significant association with LUTS, she said.

The results showing that the presence of LUTS was consistently associated with lower cognitive test scores of verbal fluency, executive function, and memory, are applicable in clinical practice, Dr. Williams said in her presentation.

“Recognizing the subtle changes in cognition among older adults with LUTS may impact treatment decisions,” she said. “For example, we can encourage and advise our patients to be physically and cognitively active and to avoid anticholinergic medications.”

Next steps for research include analyzing longitudinal changes in cognition among participants with and without LUTS, said Dr. Williams.

During a question-and-answer session, Dr. Williams agreed with a comment that incorporating cognitive screening strategies in to LUTS clinical pathways might be helpful, such as conducting a baseline Montreal Cognitive Assessment Test (MoCA) in patients with LUTS. “Periodic repeat MoCAs thereafter can help assess decline in cognition,” she said.

The study was supported by the National Institutes of Neurological Disorders and Stroke and the National Institute on Aging. The researchers had no financial conflicts to disclose.

Lower urinary tract symptoms were significantly associated with lower scores on measures of cognitive impairment in older adults, based on data from approximately 10,000 individuals.

“We know that lower urinary tract symptoms are very common in aging men and women;” however, older adults often underreport symptoms and avoid seeking treatment, Belinda Williams, MD, of the University of Alabama, Birmingham, said in a presentation at the annual meeting of the American Geriatrics Society.

“Evidence also shows us that the incidence of lower urinary tract symptoms (LUTS) is higher in patients with dementia,” she said. However, the association between cognitive impairment and LUTS has not been well studied, she said.

To address this knowledge gap, Dr. Williams and colleagues reviewed data from older adults with and without LUTS who were enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study including 30,239 Black or White adults aged 45 years and older who completed telephone or in-home assessments in 2003-2007 and in 2013-2017.

The study population included 6062 women and 4438 men who responded to questionnaires about LUTS and completed several cognitive tests via telephone in 2019-2010. The tests evaluated verbal fluency, executive function, and memory, and included the Six-Item Screener, Animal Naming, Letter F naming, and word list learning; lower scores indicated poorer cognitive performance.

Participants who met the criteria for LUTS were categorized as having mild, moderate, or severe symptoms.

The researchers controlled for age, race, education, income, and urban/rural setting in a multivariate analysis. The mean ages of the women and men were 69 years and 63 years, respectively; 41% and 32% were Black, 59% and 68% were White.

Overall, 70% of women and 62% of men reported LUTS; 6.2% and 8.2%, respectively, met criteria for cognitive impairment. The association between cognitive impairment and LUTS was statistically significant for all specific tests (P < .01), but not for the global cognitive domain tests.

Black men were more likely to report LUTS than White men, but LUTS reports were similar between Black and White women.

Moderate LUTS was the most common degree of severity for men and women (54% and 64%, respectively).

The most common symptom overall was pre-toilet leakage (urge urinary incontinence), reported by 94% of women and 91% of men. The next most common symptoms for men and women were nocturia and urgency.

“We found that, across the board, in all the cognitive tests, LUTS were associated with lower cognitive test scores,” Dr. Williams said in her presentation. Little differences were seen on the Six-Item Screener, she noted, but when they further analyzed the data using scores lower than 4 to indicate cognitive impairment, they found significant association with LUTS, she said.

The results showing that the presence of LUTS was consistently associated with lower cognitive test scores of verbal fluency, executive function, and memory, are applicable in clinical practice, Dr. Williams said in her presentation.

“Recognizing the subtle changes in cognition among older adults with LUTS may impact treatment decisions,” she said. “For example, we can encourage and advise our patients to be physically and cognitively active and to avoid anticholinergic medications.”

Next steps for research include analyzing longitudinal changes in cognition among participants with and without LUTS, said Dr. Williams.

During a question-and-answer session, Dr. Williams agreed with a comment that incorporating cognitive screening strategies in to LUTS clinical pathways might be helpful, such as conducting a baseline Montreal Cognitive Assessment Test (MoCA) in patients with LUTS. “Periodic repeat MoCAs thereafter can help assess decline in cognition,” she said.

The study was supported by the National Institutes of Neurological Disorders and Stroke and the National Institute on Aging. The researchers had no financial conflicts to disclose.

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Lower intake of dietary protein in midlife was a significant independent predictor of all-cause mortality in later life, based on data from a cohort study of more than 8000 men.

The Recommended Dietary Allowance of dietary protein intake is 0.8 g/kg body weight, but previous studies of the effect of dietary protein on all-cause mortality have yielded inconsistent results, Pedro Joaquin Ayau Aguilar, MD, of the University of Hawaii, Honolulu, said in a presentation at the annual meeting of the American Geriatrics Society.

To better examine these effects, Dr. Aguilar and colleagues reviewed data from 7486 participants in the Kuakini Honolulu Heart Program (HHP), a prospective cohort study of Japanese-American men in Hawaii.

Participants underwent a baseline exam in 1965-1968 at ages 45-68 years and were followed for mortality until December 31, 2022. The researchers created quintiles of dietary protein/kg categorized as plant or animal source, trained dietitians worked with participants to complete a 24-hour diet recall, and the primary outcome was all-cause mortality.

Overall, the mean protein intake in the study population was 1.5 g/kg body weight; the mean animal protein and plant protein intakes were 1.1 g/kg and 0.4 g/kg, respectively.

In an age-adjusted analysis, mortality rates per 1,000 person-years were significantly higher with lower total protein intake, with rates of 39.7 per 1,000 person-years and 36.8 per 1,000 person-years in the first and fifth quintiles, respectively (P < .0001).
 

Data Show Consistency Across Protein Types

Trends were similar for animal protein and plant protein intake, with mortality rates of 39.6 and 36.5 per 1000 person-years for the first and fifth quintiles, respectively.

“All of these categories had a significant trend, with the lowest quintile showing the highest mortality rate,” Dr. Aguilar said in his presentation.

The study was limited by several factors including the homogeneous population of Japanese men, and the inability to make conclusions about cause and effect, Dr. Aguilar said. However, the results were strengthened by the large cohort, long follow-up, and complete mortality surveillance, he added.

As for the study’s clinical implications, “I believe it adds to the body of evidence on how nutrition impacts health and [the data] can help us better advise our patients on their macronutrient intake to better optimize their health,” Dr. Aguilar said in a question-and-answer session following the presentation.

Looking ahead, “More research is needed to more accurately define which type of protein and in which amounts are optimal for health,” as well as how other macronutrients in different stages of life affect health span and life span, he said.

Although a minimum Recommended Daily Allowance of dietary protein is 0.8 g/kg body weight, the relationship between dietary protein intake and all-cause mortality remains unclear, said Shelly Gray, PharmD, professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

Dr. Gray, who served as a moderator for the session in which the study was presented, agreed that more research is needed before clinical implications can be discussed.

The study was supported by the Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; Kuakini Medical Center, Honolulu, Hawaii; and the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Gray had no financial conflicts to disclose.

Lower intake of dietary protein in midlife was a significant independent predictor of all-cause mortality in later life, based on data from a cohort study of more than 8000 men.

The Recommended Dietary Allowance of dietary protein intake is 0.8 g/kg body weight, but previous studies of the effect of dietary protein on all-cause mortality have yielded inconsistent results, Pedro Joaquin Ayau Aguilar, MD, of the University of Hawaii, Honolulu, said in a presentation at the annual meeting of the American Geriatrics Society.

To better examine these effects, Dr. Aguilar and colleagues reviewed data from 7486 participants in the Kuakini Honolulu Heart Program (HHP), a prospective cohort study of Japanese-American men in Hawaii.

Participants underwent a baseline exam in 1965-1968 at ages 45-68 years and were followed for mortality until December 31, 2022. The researchers created quintiles of dietary protein/kg categorized as plant or animal source, trained dietitians worked with participants to complete a 24-hour diet recall, and the primary outcome was all-cause mortality.

Overall, the mean protein intake in the study population was 1.5 g/kg body weight; the mean animal protein and plant protein intakes were 1.1 g/kg and 0.4 g/kg, respectively.

In an age-adjusted analysis, mortality rates per 1,000 person-years were significantly higher with lower total protein intake, with rates of 39.7 per 1,000 person-years and 36.8 per 1,000 person-years in the first and fifth quintiles, respectively (P < .0001).
 

Data Show Consistency Across Protein Types

Trends were similar for animal protein and plant protein intake, with mortality rates of 39.6 and 36.5 per 1000 person-years for the first and fifth quintiles, respectively.

“All of these categories had a significant trend, with the lowest quintile showing the highest mortality rate,” Dr. Aguilar said in his presentation.

The study was limited by several factors including the homogeneous population of Japanese men, and the inability to make conclusions about cause and effect, Dr. Aguilar said. However, the results were strengthened by the large cohort, long follow-up, and complete mortality surveillance, he added.

As for the study’s clinical implications, “I believe it adds to the body of evidence on how nutrition impacts health and [the data] can help us better advise our patients on their macronutrient intake to better optimize their health,” Dr. Aguilar said in a question-and-answer session following the presentation.

Looking ahead, “More research is needed to more accurately define which type of protein and in which amounts are optimal for health,” as well as how other macronutrients in different stages of life affect health span and life span, he said.

Although a minimum Recommended Daily Allowance of dietary protein is 0.8 g/kg body weight, the relationship between dietary protein intake and all-cause mortality remains unclear, said Shelly Gray, PharmD, professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

Dr. Gray, who served as a moderator for the session in which the study was presented, agreed that more research is needed before clinical implications can be discussed.

The study was supported by the Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; Kuakini Medical Center, Honolulu, Hawaii; and the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Gray had no financial conflicts to disclose.

Lower intake of dietary protein in midlife was a significant independent predictor of all-cause mortality in later life, based on data from a cohort study of more than 8000 men.

The Recommended Dietary Allowance of dietary protein intake is 0.8 g/kg body weight, but previous studies of the effect of dietary protein on all-cause mortality have yielded inconsistent results, Pedro Joaquin Ayau Aguilar, MD, of the University of Hawaii, Honolulu, said in a presentation at the annual meeting of the American Geriatrics Society.

To better examine these effects, Dr. Aguilar and colleagues reviewed data from 7486 participants in the Kuakini Honolulu Heart Program (HHP), a prospective cohort study of Japanese-American men in Hawaii.

Participants underwent a baseline exam in 1965-1968 at ages 45-68 years and were followed for mortality until December 31, 2022. The researchers created quintiles of dietary protein/kg categorized as plant or animal source, trained dietitians worked with participants to complete a 24-hour diet recall, and the primary outcome was all-cause mortality.

Overall, the mean protein intake in the study population was 1.5 g/kg body weight; the mean animal protein and plant protein intakes were 1.1 g/kg and 0.4 g/kg, respectively.

In an age-adjusted analysis, mortality rates per 1,000 person-years were significantly higher with lower total protein intake, with rates of 39.7 per 1,000 person-years and 36.8 per 1,000 person-years in the first and fifth quintiles, respectively (P < .0001).
 

Data Show Consistency Across Protein Types

Trends were similar for animal protein and plant protein intake, with mortality rates of 39.6 and 36.5 per 1000 person-years for the first and fifth quintiles, respectively.

“All of these categories had a significant trend, with the lowest quintile showing the highest mortality rate,” Dr. Aguilar said in his presentation.

The study was limited by several factors including the homogeneous population of Japanese men, and the inability to make conclusions about cause and effect, Dr. Aguilar said. However, the results were strengthened by the large cohort, long follow-up, and complete mortality surveillance, he added.

As for the study’s clinical implications, “I believe it adds to the body of evidence on how nutrition impacts health and [the data] can help us better advise our patients on their macronutrient intake to better optimize their health,” Dr. Aguilar said in a question-and-answer session following the presentation.

Looking ahead, “More research is needed to more accurately define which type of protein and in which amounts are optimal for health,” as well as how other macronutrients in different stages of life affect health span and life span, he said.

Although a minimum Recommended Daily Allowance of dietary protein is 0.8 g/kg body weight, the relationship between dietary protein intake and all-cause mortality remains unclear, said Shelly Gray, PharmD, professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

Dr. Gray, who served as a moderator for the session in which the study was presented, agreed that more research is needed before clinical implications can be discussed.

The study was supported by the Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; Kuakini Medical Center, Honolulu, Hawaii; and the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Gray had no financial conflicts to disclose.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

Medications that could have a negative effect on cognition are often used by older adults with dementia, according to data from approximately 13 million individuals presented at the annual meeting of the American Geriatrics Society.

Classes of medications including anticholinergics, antipsychotics, benzodiazepines, and non-benzodiazepine sedatives (Z drugs) have been identified as potentially inappropriate medications (PIMs) in patients with dementia, according to The American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

The medications that could worsen dementia or cognition are known as CogPIMs, said presenting author Caroline M. Mak, a doctor of pharmacy candidate at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, New York.

Previous research has characterized the prevalence of use of CogPIMs, but data connecting use of CogPIMs and healthcare use are lacking, Ms. Mak said.

Ms. Mak and colleagues conducted a cross-sectional analysis of data from 2011 to 2015 from the Medical Expenditure Panel Survey (MEPS), a national survey with data on medication and healthcare use. The researchers included approximately 13 million survey respondents older than 65 years with dementia.

Exposure to CogPIMs was defined as filling a prescription for one or more of the CogPIMs during the study period. Population estimates of the prevalence of use of the CogPIMs were created using survey-weighted procedures, and prevalence trends were assessed using the Cochran-Armitage test.

Overall, the prevalence was 15.9%, 11.5%, 7.5%, and 3.8% for use of benzodiazepines, anticholinergics, antipsychotics, and Z drugs, respectively, during the study period.

Of these, benzodiazepines showed a significant trend with an increase in prevalence from 8.9% in 2011 to 16.4% in 2015 (P = .02).

The odds of hospitalization were more than twice as likely in individuals who reported using Z drugs (odds ratio, 2.57; P = .02) based on logistic regression. In addition, exposure to antipsychotics was significantly associated with an increased rate of hospitalization based on a binomial model for incidence rate ratio (IRR, 1.51; P = .02).

The findings were limited by several factors including the cross-sectional design, reliance on self-reports, and the lack of more recent data.

However, the results show that CogPIMs are often used by older adults with dementia, and antipsychotics and Z drugs could be targets for interventions to prevent harm from medication interactions and side effects, the researchers concluded.
 

Findings Highlight Need for Drug Awareness

The current study is important because of the expansion in the aging population and an increase in the number of patients with dementia, Ms. Mak said in an interview. “In both our older population and dementia patients, there are certain medication considerations that we need to take into account, and certain drugs that should be avoided if possible,” she said. Clinicians have been trying to use the Beers criteria to reduce potential medication harm, she noted. “One group of investigators (Hilmer et al.), has proposed a narrower focus on anticholinergic and sedative/hypnotic medication in the Drug Burden Index (DBI); the CogPIMs are a subset of both approaches (Beers and DBI) and represent a collection of medications that pose potential risks to our patients,” said Ms. Mak.

Continued reassessment is needed on appropriateness of anticholinergics, Z drugs, benzodiazepines, and antipsychotics in older patients with dementia, she added.

“Even though the only group to have a significant increase in prevalence [of use] was the benzodiazepine group, we didn’t see a decrease in any of the other groups,” said Ms. Mak. The current research provides a benchmark for CogPIMs use that can be monitored in the future for increases or, ideally, decreases, she said.
 

Part of a Bigger Picture

The current study is part of the work of Team Alice, a national deprescribing group affiliated with the University at Buffalo that was inspired by the tragic death of Alice Brennan, triggered by preventable medication harm, Ms. Mak said in an interview. “Team Alice consists of an array of academic, primary care, health plan, and regional health information partners that have designed patient-driven interventions to reduce medication harm, especially within primary care settings,” she said. “Their mission is to save people like Alice by pursuing multiple strategies to deprescribe unsafe medication, reduce harm, and foster successful aging. By characterizing the use of CogPIMs, we can design better intervention strategies,” she said.

Although Ms. Mak was not surprised by the emergence of benzodiazepines as the most commonly used drug groups, she was surprised by the increase during the study period.

“Unfortunately, our dataset was not rich enough to include reasons for this increase,” she said. In practice, “I have seen patients getting short-term, as needed, prescriptions for a benzodiazepine to address the anxiety and/or insomnia after the loss of a loved one; this may account for a small proportion of benzodiazepine use that appears to be inappropriate because of a lack of associated appropriate diagnosis,” she noted.

Also, the findings of increased hospitalization associated with Z drugs raises concerns, Ms. Mak said. Although the findings are consistent with other research, they illustrate the need for further investigation to identify strategies to prevent this harm, she said. “Not finding associations with hospitalization related to benzodiazepine or anticholinergics was a mild surprise,” Ms. Mak said in an interview. “However, while we know that these drugs can have a negative effect on older people, the effects may not have been severe enough to result in hospitalizations,” she said.

Looking ahead, Ms. Mak said she would like to see the study rerun with a more current data set, especially with regard to benzodiazepines and antipsychotics.
 

Seek Strategies to Reduce Medication Use

The current study was notable for its community-based population and attention to hospitalizations, Shelly Gray, PharmD, a professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

“Most studies examining potentially inappropriate medications that may impair cognition have been conducted in nursing homes, while this study focuses on community dwelling older adults where most people with dementia live,” said Dr. Gray, who served as a moderator for the session in which the study was presented.

In addition, “A unique aspect of this study was to examine how these medications are related to hospitalizations,” she said.

Given recent efforts to reduce use of potentially inappropriate medications in people with dementia, the increase in prevalence of use over the study period was surprising, especially for benzodiazepines, said Dr. Gray.

In clinical practice, “health care providers should continue to look for opportunities to deprescribe medications that may worsen cognition in people with dementia,” she said. However, more research is needed to examine trends in the years beyond 2015 for a more contemporary picture of medication use in this population, she noted.

The study received no outside funding. The researchers and Dr. Gray had no financial conflicts to disclose.

Medications that could have a negative effect on cognition are often used by older adults with dementia, according to data from approximately 13 million individuals presented at the annual meeting of the American Geriatrics Society.

Classes of medications including anticholinergics, antipsychotics, benzodiazepines, and non-benzodiazepine sedatives (Z drugs) have been identified as potentially inappropriate medications (PIMs) in patients with dementia, according to The American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

The medications that could worsen dementia or cognition are known as CogPIMs, said presenting author Caroline M. Mak, a doctor of pharmacy candidate at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, New York.

Previous research has characterized the prevalence of use of CogPIMs, but data connecting use of CogPIMs and healthcare use are lacking, Ms. Mak said.

Ms. Mak and colleagues conducted a cross-sectional analysis of data from 2011 to 2015 from the Medical Expenditure Panel Survey (MEPS), a national survey with data on medication and healthcare use. The researchers included approximately 13 million survey respondents older than 65 years with dementia.

Exposure to CogPIMs was defined as filling a prescription for one or more of the CogPIMs during the study period. Population estimates of the prevalence of use of the CogPIMs were created using survey-weighted procedures, and prevalence trends were assessed using the Cochran-Armitage test.

Overall, the prevalence was 15.9%, 11.5%, 7.5%, and 3.8% for use of benzodiazepines, anticholinergics, antipsychotics, and Z drugs, respectively, during the study period.

Of these, benzodiazepines showed a significant trend with an increase in prevalence from 8.9% in 2011 to 16.4% in 2015 (P = .02).

The odds of hospitalization were more than twice as likely in individuals who reported using Z drugs (odds ratio, 2.57; P = .02) based on logistic regression. In addition, exposure to antipsychotics was significantly associated with an increased rate of hospitalization based on a binomial model for incidence rate ratio (IRR, 1.51; P = .02).

The findings were limited by several factors including the cross-sectional design, reliance on self-reports, and the lack of more recent data.

However, the results show that CogPIMs are often used by older adults with dementia, and antipsychotics and Z drugs could be targets for interventions to prevent harm from medication interactions and side effects, the researchers concluded.
 

Findings Highlight Need for Drug Awareness

The current study is important because of the expansion in the aging population and an increase in the number of patients with dementia, Ms. Mak said in an interview. “In both our older population and dementia patients, there are certain medication considerations that we need to take into account, and certain drugs that should be avoided if possible,” she said. Clinicians have been trying to use the Beers criteria to reduce potential medication harm, she noted. “One group of investigators (Hilmer et al.), has proposed a narrower focus on anticholinergic and sedative/hypnotic medication in the Drug Burden Index (DBI); the CogPIMs are a subset of both approaches (Beers and DBI) and represent a collection of medications that pose potential risks to our patients,” said Ms. Mak.

Continued reassessment is needed on appropriateness of anticholinergics, Z drugs, benzodiazepines, and antipsychotics in older patients with dementia, she added.

“Even though the only group to have a significant increase in prevalence [of use] was the benzodiazepine group, we didn’t see a decrease in any of the other groups,” said Ms. Mak. The current research provides a benchmark for CogPIMs use that can be monitored in the future for increases or, ideally, decreases, she said.
 

Part of a Bigger Picture

The current study is part of the work of Team Alice, a national deprescribing group affiliated with the University at Buffalo that was inspired by the tragic death of Alice Brennan, triggered by preventable medication harm, Ms. Mak said in an interview. “Team Alice consists of an array of academic, primary care, health plan, and regional health information partners that have designed patient-driven interventions to reduce medication harm, especially within primary care settings,” she said. “Their mission is to save people like Alice by pursuing multiple strategies to deprescribe unsafe medication, reduce harm, and foster successful aging. By characterizing the use of CogPIMs, we can design better intervention strategies,” she said.

Although Ms. Mak was not surprised by the emergence of benzodiazepines as the most commonly used drug groups, she was surprised by the increase during the study period.

“Unfortunately, our dataset was not rich enough to include reasons for this increase,” she said. In practice, “I have seen patients getting short-term, as needed, prescriptions for a benzodiazepine to address the anxiety and/or insomnia after the loss of a loved one; this may account for a small proportion of benzodiazepine use that appears to be inappropriate because of a lack of associated appropriate diagnosis,” she noted.

Also, the findings of increased hospitalization associated with Z drugs raises concerns, Ms. Mak said. Although the findings are consistent with other research, they illustrate the need for further investigation to identify strategies to prevent this harm, she said. “Not finding associations with hospitalization related to benzodiazepine or anticholinergics was a mild surprise,” Ms. Mak said in an interview. “However, while we know that these drugs can have a negative effect on older people, the effects may not have been severe enough to result in hospitalizations,” she said.

Looking ahead, Ms. Mak said she would like to see the study rerun with a more current data set, especially with regard to benzodiazepines and antipsychotics.
 

Seek Strategies to Reduce Medication Use

The current study was notable for its community-based population and attention to hospitalizations, Shelly Gray, PharmD, a professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

“Most studies examining potentially inappropriate medications that may impair cognition have been conducted in nursing homes, while this study focuses on community dwelling older adults where most people with dementia live,” said Dr. Gray, who served as a moderator for the session in which the study was presented.

In addition, “A unique aspect of this study was to examine how these medications are related to hospitalizations,” she said.

Given recent efforts to reduce use of potentially inappropriate medications in people with dementia, the increase in prevalence of use over the study period was surprising, especially for benzodiazepines, said Dr. Gray.

In clinical practice, “health care providers should continue to look for opportunities to deprescribe medications that may worsen cognition in people with dementia,” she said. However, more research is needed to examine trends in the years beyond 2015 for a more contemporary picture of medication use in this population, she noted.

The study received no outside funding. The researchers and Dr. Gray had no financial conflicts to disclose.

Medications that could have a negative effect on cognition are often used by older adults with dementia, according to data from approximately 13 million individuals presented at the annual meeting of the American Geriatrics Society.

Classes of medications including anticholinergics, antipsychotics, benzodiazepines, and non-benzodiazepine sedatives (Z drugs) have been identified as potentially inappropriate medications (PIMs) in patients with dementia, according to The American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

The medications that could worsen dementia or cognition are known as CogPIMs, said presenting author Caroline M. Mak, a doctor of pharmacy candidate at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, New York.

Previous research has characterized the prevalence of use of CogPIMs, but data connecting use of CogPIMs and healthcare use are lacking, Ms. Mak said.

Ms. Mak and colleagues conducted a cross-sectional analysis of data from 2011 to 2015 from the Medical Expenditure Panel Survey (MEPS), a national survey with data on medication and healthcare use. The researchers included approximately 13 million survey respondents older than 65 years with dementia.

Exposure to CogPIMs was defined as filling a prescription for one or more of the CogPIMs during the study period. Population estimates of the prevalence of use of the CogPIMs were created using survey-weighted procedures, and prevalence trends were assessed using the Cochran-Armitage test.

Overall, the prevalence was 15.9%, 11.5%, 7.5%, and 3.8% for use of benzodiazepines, anticholinergics, antipsychotics, and Z drugs, respectively, during the study period.

Of these, benzodiazepines showed a significant trend with an increase in prevalence from 8.9% in 2011 to 16.4% in 2015 (P = .02).

The odds of hospitalization were more than twice as likely in individuals who reported using Z drugs (odds ratio, 2.57; P = .02) based on logistic regression. In addition, exposure to antipsychotics was significantly associated with an increased rate of hospitalization based on a binomial model for incidence rate ratio (IRR, 1.51; P = .02).

The findings were limited by several factors including the cross-sectional design, reliance on self-reports, and the lack of more recent data.

However, the results show that CogPIMs are often used by older adults with dementia, and antipsychotics and Z drugs could be targets for interventions to prevent harm from medication interactions and side effects, the researchers concluded.
 

Findings Highlight Need for Drug Awareness

The current study is important because of the expansion in the aging population and an increase in the number of patients with dementia, Ms. Mak said in an interview. “In both our older population and dementia patients, there are certain medication considerations that we need to take into account, and certain drugs that should be avoided if possible,” she said. Clinicians have been trying to use the Beers criteria to reduce potential medication harm, she noted. “One group of investigators (Hilmer et al.), has proposed a narrower focus on anticholinergic and sedative/hypnotic medication in the Drug Burden Index (DBI); the CogPIMs are a subset of both approaches (Beers and DBI) and represent a collection of medications that pose potential risks to our patients,” said Ms. Mak.

Continued reassessment is needed on appropriateness of anticholinergics, Z drugs, benzodiazepines, and antipsychotics in older patients with dementia, she added.

“Even though the only group to have a significant increase in prevalence [of use] was the benzodiazepine group, we didn’t see a decrease in any of the other groups,” said Ms. Mak. The current research provides a benchmark for CogPIMs use that can be monitored in the future for increases or, ideally, decreases, she said.
 

Part of a Bigger Picture

The current study is part of the work of Team Alice, a national deprescribing group affiliated with the University at Buffalo that was inspired by the tragic death of Alice Brennan, triggered by preventable medication harm, Ms. Mak said in an interview. “Team Alice consists of an array of academic, primary care, health plan, and regional health information partners that have designed patient-driven interventions to reduce medication harm, especially within primary care settings,” she said. “Their mission is to save people like Alice by pursuing multiple strategies to deprescribe unsafe medication, reduce harm, and foster successful aging. By characterizing the use of CogPIMs, we can design better intervention strategies,” she said.

Although Ms. Mak was not surprised by the emergence of benzodiazepines as the most commonly used drug groups, she was surprised by the increase during the study period.

“Unfortunately, our dataset was not rich enough to include reasons for this increase,” she said. In practice, “I have seen patients getting short-term, as needed, prescriptions for a benzodiazepine to address the anxiety and/or insomnia after the loss of a loved one; this may account for a small proportion of benzodiazepine use that appears to be inappropriate because of a lack of associated appropriate diagnosis,” she noted.

Also, the findings of increased hospitalization associated with Z drugs raises concerns, Ms. Mak said. Although the findings are consistent with other research, they illustrate the need for further investigation to identify strategies to prevent this harm, she said. “Not finding associations with hospitalization related to benzodiazepine or anticholinergics was a mild surprise,” Ms. Mak said in an interview. “However, while we know that these drugs can have a negative effect on older people, the effects may not have been severe enough to result in hospitalizations,” she said.

Looking ahead, Ms. Mak said she would like to see the study rerun with a more current data set, especially with regard to benzodiazepines and antipsychotics.
 

Seek Strategies to Reduce Medication Use

The current study was notable for its community-based population and attention to hospitalizations, Shelly Gray, PharmD, a professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

“Most studies examining potentially inappropriate medications that may impair cognition have been conducted in nursing homes, while this study focuses on community dwelling older adults where most people with dementia live,” said Dr. Gray, who served as a moderator for the session in which the study was presented.

In addition, “A unique aspect of this study was to examine how these medications are related to hospitalizations,” she said.

Given recent efforts to reduce use of potentially inappropriate medications in people with dementia, the increase in prevalence of use over the study period was surprising, especially for benzodiazepines, said Dr. Gray.

In clinical practice, “health care providers should continue to look for opportunities to deprescribe medications that may worsen cognition in people with dementia,” she said. However, more research is needed to examine trends in the years beyond 2015 for a more contemporary picture of medication use in this population, she noted.

The study received no outside funding. The researchers and Dr. Gray had no financial conflicts to disclose.

Clinical guidelines on age-related hearing loss (ARHL), published in Otolaryngology–Head and Neck Surgery, highlight referral recommendations for all clinicians, including primary care doctors, who often are the first clinicians to screen for and address the condition.

Betty S. Tsai Do, MD, with the department of head & neck surgery at Kaiser Permanente in Walnut Creek, California, is the first author for the guidelines, which recommend screening patients 50 years or older at the time of a healthcare encounter. They also detail when to test and refer.
 

Three ‘Strong Recommendations’

Three of the action points are labeled “strong recommendations.” They are:

• If screening suggests hearing loss, clinicians should conduct an audiogram or refer to a clinician who can conduct one.
• Clinicians should offer, or refer to a specialist who can offer, appropriately fit amplification, such as hearing aids.
• If patients have appropriately fit amplification and still have trouble with hearing and understanding speech, clinicians should refer patients to see if they are good candidates for a cochlear implant.

The authors note that ARHL is the most common sensory deficit seen in older patients, but it is underdiagnosed and undertreated. “Between ages 65 and 74, one in three adults experience hearing loss and almost 50% of those 75 years of age or older will report hearing loss according to the National Institute on Deafness and Other Communication Disorders.” Consequences of the untreated deficit, in addition to limiting ability to communicate, include higher risk of dementia, cardiovascular disease, depression, falls, and workplace marginalization.

Until now, there have been no evidence-based clinical guidelines on when to screen, test, and refer. Though previously proposed quality improvement measures have defined ARHL as starting at age 60, these guidelines include those 50 and older to promote earlier detection.
 

Guidelines Only Part of the Solution

While the guidelines are a step in the right direction, they won’t address some persistent barriers to changing practice, said Michael McKee, MD, MPH, a family medicine physician and co-director of the Center for Disability Health and Wellness at the University of Michigan in Ann Arbor, who was not part of the guideline team.

“I think [the guidelines] will raise the awareness on why it’s important to address hearing loss,” he says. “Many primary care providers don’t elevate hearing loss as a priority topic. The problem is that we’re struggling with getting things in place to have a more supportive system to carry out those recommendations.”
 

Lack of Training and Support

The problems include lack of training on hearing loss for physicians, starting with medical school. Another complication is time: A conversation about hearing loss adds to the multitude of conversations a primary care provider is expected to have with their patients in a short visit.

Additionally, when hearing loss is suspected, an audiologist may be hard to find to perform the audiogram, Dr. McKee says. If patients agree to see an audiologist and that specialist finds hearing loss, patients may not want to wear a device due to stigma or may not be able to afford a device that will fit properly and truly benefit them because Medicare does not cover hearing aids.

“Only about 20-plus percent of those eligible for hearing aids get them,” he said. Hearing aids available over the counter help some people, but may be difficult to fit properly and may be hard for some to use correctly, he added.

“That comes back to the primary care provider, so it’s unfortunately a very unsatisfying course,” he said.
 

‘Primary Care Providers Do Value Guidelines’

However, “Primary care providers do value guidelines. They do value strong recommendations,” he said. We are trying to figure out how we can support people with unaddressed hearing loss in the primary care setting, Dr. McKee said. “Once we get there, we need to advocate for an expansion of coverage,” he said.

The authors note that the messages in the guidelines are important for all clinicians.

“The impact of hearing loss and screening should not be the sole responsibility of an audiologist, an otolaryngologist, nor primary care provider. Any time and place that a patient interacts with the healthcare system is an opportunity for preventive healthcare, such as hearing screening, to occur,” they write.

Funding for this research was provided by the American Academy of Otolaryngology–Head and Neck Surgery Foundation. Dr. Do and Dr. McKee report no relevant financial relationships. Full disclosures of the co-authors are listed with the full text of the paper.
 

Clinical guidelines on age-related hearing loss (ARHL), published in Otolaryngology–Head and Neck Surgery, highlight referral recommendations for all clinicians, including primary care doctors, who often are the first clinicians to screen for and address the condition.

Betty S. Tsai Do, MD, with the department of head & neck surgery at Kaiser Permanente in Walnut Creek, California, is the first author for the guidelines, which recommend screening patients 50 years or older at the time of a healthcare encounter. They also detail when to test and refer.
 

Three ‘Strong Recommendations’

Three of the action points are labeled “strong recommendations.” They are:

• If screening suggests hearing loss, clinicians should conduct an audiogram or refer to a clinician who can conduct one.
• Clinicians should offer, or refer to a specialist who can offer, appropriately fit amplification, such as hearing aids.
• If patients have appropriately fit amplification and still have trouble with hearing and understanding speech, clinicians should refer patients to see if they are good candidates for a cochlear implant.

The authors note that ARHL is the most common sensory deficit seen in older patients, but it is underdiagnosed and undertreated. “Between ages 65 and 74, one in three adults experience hearing loss and almost 50% of those 75 years of age or older will report hearing loss according to the National Institute on Deafness and Other Communication Disorders.” Consequences of the untreated deficit, in addition to limiting ability to communicate, include higher risk of dementia, cardiovascular disease, depression, falls, and workplace marginalization.

Until now, there have been no evidence-based clinical guidelines on when to screen, test, and refer. Though previously proposed quality improvement measures have defined ARHL as starting at age 60, these guidelines include those 50 and older to promote earlier detection.
 

Guidelines Only Part of the Solution

While the guidelines are a step in the right direction, they won’t address some persistent barriers to changing practice, said Michael McKee, MD, MPH, a family medicine physician and co-director of the Center for Disability Health and Wellness at the University of Michigan in Ann Arbor, who was not part of the guideline team.

“I think [the guidelines] will raise the awareness on why it’s important to address hearing loss,” he says. “Many primary care providers don’t elevate hearing loss as a priority topic. The problem is that we’re struggling with getting things in place to have a more supportive system to carry out those recommendations.”
 

Lack of Training and Support

The problems include lack of training on hearing loss for physicians, starting with medical school. Another complication is time: A conversation about hearing loss adds to the multitude of conversations a primary care provider is expected to have with their patients in a short visit.

Additionally, when hearing loss is suspected, an audiologist may be hard to find to perform the audiogram, Dr. McKee says. If patients agree to see an audiologist and that specialist finds hearing loss, patients may not want to wear a device due to stigma or may not be able to afford a device that will fit properly and truly benefit them because Medicare does not cover hearing aids.

“Only about 20-plus percent of those eligible for hearing aids get them,” he said. Hearing aids available over the counter help some people, but may be difficult to fit properly and may be hard for some to use correctly, he added.

“That comes back to the primary care provider, so it’s unfortunately a very unsatisfying course,” he said.
 

‘Primary Care Providers Do Value Guidelines’

However, “Primary care providers do value guidelines. They do value strong recommendations,” he said. We are trying to figure out how we can support people with unaddressed hearing loss in the primary care setting, Dr. McKee said. “Once we get there, we need to advocate for an expansion of coverage,” he said.

The authors note that the messages in the guidelines are important for all clinicians.

“The impact of hearing loss and screening should not be the sole responsibility of an audiologist, an otolaryngologist, nor primary care provider. Any time and place that a patient interacts with the healthcare system is an opportunity for preventive healthcare, such as hearing screening, to occur,” they write.

Funding for this research was provided by the American Academy of Otolaryngology–Head and Neck Surgery Foundation. Dr. Do and Dr. McKee report no relevant financial relationships. Full disclosures of the co-authors are listed with the full text of the paper.
 

Clinical guidelines on age-related hearing loss (ARHL), published in Otolaryngology–Head and Neck Surgery, highlight referral recommendations for all clinicians, including primary care doctors, who often are the first clinicians to screen for and address the condition.

Betty S. Tsai Do, MD, with the department of head & neck surgery at Kaiser Permanente in Walnut Creek, California, is the first author for the guidelines, which recommend screening patients 50 years or older at the time of a healthcare encounter. They also detail when to test and refer.
 

Three ‘Strong Recommendations’

Three of the action points are labeled “strong recommendations.” They are:

• If screening suggests hearing loss, clinicians should conduct an audiogram or refer to a clinician who can conduct one.
• Clinicians should offer, or refer to a specialist who can offer, appropriately fit amplification, such as hearing aids.
• If patients have appropriately fit amplification and still have trouble with hearing and understanding speech, clinicians should refer patients to see if they are good candidates for a cochlear implant.

The authors note that ARHL is the most common sensory deficit seen in older patients, but it is underdiagnosed and undertreated. “Between ages 65 and 74, one in three adults experience hearing loss and almost 50% of those 75 years of age or older will report hearing loss according to the National Institute on Deafness and Other Communication Disorders.” Consequences of the untreated deficit, in addition to limiting ability to communicate, include higher risk of dementia, cardiovascular disease, depression, falls, and workplace marginalization.

Until now, there have been no evidence-based clinical guidelines on when to screen, test, and refer. Though previously proposed quality improvement measures have defined ARHL as starting at age 60, these guidelines include those 50 and older to promote earlier detection.
 

Guidelines Only Part of the Solution

While the guidelines are a step in the right direction, they won’t address some persistent barriers to changing practice, said Michael McKee, MD, MPH, a family medicine physician and co-director of the Center for Disability Health and Wellness at the University of Michigan in Ann Arbor, who was not part of the guideline team.

“I think [the guidelines] will raise the awareness on why it’s important to address hearing loss,” he says. “Many primary care providers don’t elevate hearing loss as a priority topic. The problem is that we’re struggling with getting things in place to have a more supportive system to carry out those recommendations.”
 

Lack of Training and Support

The problems include lack of training on hearing loss for physicians, starting with medical school. Another complication is time: A conversation about hearing loss adds to the multitude of conversations a primary care provider is expected to have with their patients in a short visit.

Additionally, when hearing loss is suspected, an audiologist may be hard to find to perform the audiogram, Dr. McKee says. If patients agree to see an audiologist and that specialist finds hearing loss, patients may not want to wear a device due to stigma or may not be able to afford a device that will fit properly and truly benefit them because Medicare does not cover hearing aids.

“Only about 20-plus percent of those eligible for hearing aids get them,” he said. Hearing aids available over the counter help some people, but may be difficult to fit properly and may be hard for some to use correctly, he added.

“That comes back to the primary care provider, so it’s unfortunately a very unsatisfying course,” he said.
 

‘Primary Care Providers Do Value Guidelines’

However, “Primary care providers do value guidelines. They do value strong recommendations,” he said. We are trying to figure out how we can support people with unaddressed hearing loss in the primary care setting, Dr. McKee said. “Once we get there, we need to advocate for an expansion of coverage,” he said.

The authors note that the messages in the guidelines are important for all clinicians.

“The impact of hearing loss and screening should not be the sole responsibility of an audiologist, an otolaryngologist, nor primary care provider. Any time and place that a patient interacts with the healthcare system is an opportunity for preventive healthcare, such as hearing screening, to occur,” they write.

Funding for this research was provided by the American Academy of Otolaryngology–Head and Neck Surgery Foundation. Dr. Do and Dr. McKee report no relevant financial relationships. Full disclosures of the co-authors are listed with the full text of the paper.