Women who have taken hormone replacement therapy for menopausal symptoms will be relieved by findings from a large British case-control study reporting no overall increased risk of dementia as long as exposure is not long term.

Publishing results online Sept. 29 in BMJ, ( Yana Vinogradova, PhD, a senior research fellow at the University of Nottingham (England), and colleagues made this observation after conducting nested case-control studies involving more than 700,000 women in two U.K. primary care databases. The investigators undertook the study to clarify disparate findings over the past 2 decades on dementia risk associated with menopausal hormone replacement,

“The findings show that menopausal hormone therapy, or MHT, is generally safe for women who require it,” Dr. Vinogradova said in an interview. “A small risk association was found for future development of Alzheimer’s disease increasing with the length of menopausal hormone treatment.” This finding applied only to combined treatments of estrogen plus progestin and became measurable only after long-term use of 5 years or more. “These risk associations, only for long-term use of MHT, are in line with findings related to breast cancer risk,” she said.

The findings also align with previous biological speculations that estrogen combined with progestin may have a harmful effect on the aging brain, she added, “but we also cannot completely rule out other possible factors from our study. For example, some women who were in fact suffering from early signs of Alzheimer’s disease similar to menopausal symptoms may have continued with their menopausal therapy for longer than other women.”

Concerns about the risk of dementia with MHT date back to 2003 when data from the Women’s Health Initiative Memory Study showed that incidence of all-cause dementia doubled in women age 65 years and older after treatment with conjugated equine estrogens and medroxyprogesterone acetate for an average of 4 years. More recently, Finnish research has yielded conflicting data about risks.

The study

The investigators used two U.K. primary care databases (QResearch and CPRD) to analyze MHT prescriptions for 118,501 women age 55 and older diagnosed with dementia between 1998 and 2020 and 497,416 female controls matched by age and general practice, but with no record of dementia.

The cohort was older: mean age of cases was 83.5 years and mean duration of treatment was 16 years for an average age of 67.7 at first captured prescription, considerably later than when most women begin MHT. Relevant factors such as family history, smoking, alcohol consumption, preexisting conditions, and other prescribed drugs were taken into account.

Overall, 16,291 (14%) dementia cases and 68,726 (14%) controls had been exposed to MHT in the period up to 3 years before diagnosis.

After adjusting for potentially confounding factors, the researchers found no overall associations between hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment. Within the subgroup of women younger than 80 years who had been taking estrogen-only therapy for 10 years or more, a slightly decreased risk of dementia emerged: odds ratio, 0.85; 95% confidence interval, 0.76-0.94.

However, an analysis of dementia cases with a diagnosis specifically of Alzheimer’s disease showed a slight increase in risk associated with estrogen-progestin therapy. Increased risks of developing specifically Alzheimer’s disease emerged in those who had used combination therapy for 5-9 years (OR, 1.11; 95% CI, 1.04-1.20) and also for 10 years or more (OR, 1.19; 95% CI, 1.06-1.33). This risk rose gradually with each year of exposure, reaching an average 11% increased risk for use from 5-9 years and an average 19% for use 10 years or more – equivalent to, respectively, five and seven extra cases per 10,000 woman-years.

According to Jill M. Rabin, MD, a professor at the Feinstein Institutes for Medical Research and an ob.gyn. with Northwell Health in Manhasset, N.Y., the findings make sense for two reasons. “First, there are other health issues noted in women taking long-term combination hormonal therapy such as an increased risk of breast cancer,” she said in an interview. “Second, progesterone is recommended for women who have retained their uterus in order to counteract the potential effects of estrogen on the uterine lining causing possible overgrowth. There are systemic effects however of progesterone, as it counteracts estrogen, potentially decreasing its benefit on the neurological system.”

She added that this analysis is synchronous with other biological studies demonstrating possible neuroprotective effects of estrogen on the brain, especially among younger women. “The vascular system in the newly menopausal female is noted to have less endothelial and intimal thickening, better blood flow and oxygenation, and in general less vascular damage. Estrogen in these relatively younger, newly menopausal women may help to stabilize the vasculature as well as the neurologic system. On the other hand, estrogen therapy over the age of 80 may be delivered to a neurovasculature damaged with age and time, may be somewhat less beneficial.” Older women also have fewer estrogen receptors and, in general, other medical comorbidities.

According to the authors, the findings will be helpful to policy-makers, doctors, and patients when making choices about hormone therapy.

In an accompanying editorial, two U.S. researchers called the findings reassuring. Pauline M. Maki, PhD, of the University of Illinois at Chicago, and JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health in Boston, however, pointed out that the current study with its older cohort and older age at MHT initiation could not address the important issue of the “timing hypothesis” – namely, that earlier initiation of hormone therapy might confer greater protection against Alzheimer’s disease, compared with later use.

And while the current observations do not change the recommendation that MHT should not be used to prevent dementia, they are helpful for providers to put dementia findings in context for patients. “The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they wrote.

This study was funded by the U.K. National Institute for Health Research School for Primary Care Research.

Coauthor Dr. Julia Hippisley-Cox is a director of QResearch, EMIS Health, which supplies the QResearch database used for this work, and is a founder and shareholder of ClinRisk., which produces software to implement clinical risk algorithms.

Women who have taken hormone replacement therapy for menopausal symptoms will be relieved by findings from a large British case-control study reporting no overall increased risk of dementia as long as exposure is not long term.

Publishing results online Sept. 29 in BMJ, ( Yana Vinogradova, PhD, a senior research fellow at the University of Nottingham (England), and colleagues made this observation after conducting nested case-control studies involving more than 700,000 women in two U.K. primary care databases. The investigators undertook the study to clarify disparate findings over the past 2 decades on dementia risk associated with menopausal hormone replacement,

“The findings show that menopausal hormone therapy, or MHT, is generally safe for women who require it,” Dr. Vinogradova said in an interview. “A small risk association was found for future development of Alzheimer’s disease increasing with the length of menopausal hormone treatment.” This finding applied only to combined treatments of estrogen plus progestin and became measurable only after long-term use of 5 years or more. “These risk associations, only for long-term use of MHT, are in line with findings related to breast cancer risk,” she said.

The findings also align with previous biological speculations that estrogen combined with progestin may have a harmful effect on the aging brain, she added, “but we also cannot completely rule out other possible factors from our study. For example, some women who were in fact suffering from early signs of Alzheimer’s disease similar to menopausal symptoms may have continued with their menopausal therapy for longer than other women.”

Concerns about the risk of dementia with MHT date back to 2003 when data from the Women’s Health Initiative Memory Study showed that incidence of all-cause dementia doubled in women age 65 years and older after treatment with conjugated equine estrogens and medroxyprogesterone acetate for an average of 4 years. More recently, Finnish research has yielded conflicting data about risks.

The study

The investigators used two U.K. primary care databases (QResearch and CPRD) to analyze MHT prescriptions for 118,501 women age 55 and older diagnosed with dementia between 1998 and 2020 and 497,416 female controls matched by age and general practice, but with no record of dementia.

The cohort was older: mean age of cases was 83.5 years and mean duration of treatment was 16 years for an average age of 67.7 at first captured prescription, considerably later than when most women begin MHT. Relevant factors such as family history, smoking, alcohol consumption, preexisting conditions, and other prescribed drugs were taken into account.

Overall, 16,291 (14%) dementia cases and 68,726 (14%) controls had been exposed to MHT in the period up to 3 years before diagnosis.

After adjusting for potentially confounding factors, the researchers found no overall associations between hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment. Within the subgroup of women younger than 80 years who had been taking estrogen-only therapy for 10 years or more, a slightly decreased risk of dementia emerged: odds ratio, 0.85; 95% confidence interval, 0.76-0.94.

However, an analysis of dementia cases with a diagnosis specifically of Alzheimer’s disease showed a slight increase in risk associated with estrogen-progestin therapy. Increased risks of developing specifically Alzheimer’s disease emerged in those who had used combination therapy for 5-9 years (OR, 1.11; 95% CI, 1.04-1.20) and also for 10 years or more (OR, 1.19; 95% CI, 1.06-1.33). This risk rose gradually with each year of exposure, reaching an average 11% increased risk for use from 5-9 years and an average 19% for use 10 years or more – equivalent to, respectively, five and seven extra cases per 10,000 woman-years.

According to Jill M. Rabin, MD, a professor at the Feinstein Institutes for Medical Research and an ob.gyn. with Northwell Health in Manhasset, N.Y., the findings make sense for two reasons. “First, there are other health issues noted in women taking long-term combination hormonal therapy such as an increased risk of breast cancer,” she said in an interview. “Second, progesterone is recommended for women who have retained their uterus in order to counteract the potential effects of estrogen on the uterine lining causing possible overgrowth. There are systemic effects however of progesterone, as it counteracts estrogen, potentially decreasing its benefit on the neurological system.”

She added that this analysis is synchronous with other biological studies demonstrating possible neuroprotective effects of estrogen on the brain, especially among younger women. “The vascular system in the newly menopausal female is noted to have less endothelial and intimal thickening, better blood flow and oxygenation, and in general less vascular damage. Estrogen in these relatively younger, newly menopausal women may help to stabilize the vasculature as well as the neurologic system. On the other hand, estrogen therapy over the age of 80 may be delivered to a neurovasculature damaged with age and time, may be somewhat less beneficial.” Older women also have fewer estrogen receptors and, in general, other medical comorbidities.

According to the authors, the findings will be helpful to policy-makers, doctors, and patients when making choices about hormone therapy.

In an accompanying editorial, two U.S. researchers called the findings reassuring. Pauline M. Maki, PhD, of the University of Illinois at Chicago, and JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health in Boston, however, pointed out that the current study with its older cohort and older age at MHT initiation could not address the important issue of the “timing hypothesis” – namely, that earlier initiation of hormone therapy might confer greater protection against Alzheimer’s disease, compared with later use.

And while the current observations do not change the recommendation that MHT should not be used to prevent dementia, they are helpful for providers to put dementia findings in context for patients. “The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they wrote.

This study was funded by the U.K. National Institute for Health Research School for Primary Care Research.

Coauthor Dr. Julia Hippisley-Cox is a director of QResearch, EMIS Health, which supplies the QResearch database used for this work, and is a founder and shareholder of ClinRisk., which produces software to implement clinical risk algorithms.

Women who have taken hormone replacement therapy for menopausal symptoms will be relieved by findings from a large British case-control study reporting no overall increased risk of dementia as long as exposure is not long term.

Publishing results online Sept. 29 in BMJ, ( Yana Vinogradova, PhD, a senior research fellow at the University of Nottingham (England), and colleagues made this observation after conducting nested case-control studies involving more than 700,000 women in two U.K. primary care databases. The investigators undertook the study to clarify disparate findings over the past 2 decades on dementia risk associated with menopausal hormone replacement,

“The findings show that menopausal hormone therapy, or MHT, is generally safe for women who require it,” Dr. Vinogradova said in an interview. “A small risk association was found for future development of Alzheimer’s disease increasing with the length of menopausal hormone treatment.” This finding applied only to combined treatments of estrogen plus progestin and became measurable only after long-term use of 5 years or more. “These risk associations, only for long-term use of MHT, are in line with findings related to breast cancer risk,” she said.

The findings also align with previous biological speculations that estrogen combined with progestin may have a harmful effect on the aging brain, she added, “but we also cannot completely rule out other possible factors from our study. For example, some women who were in fact suffering from early signs of Alzheimer’s disease similar to menopausal symptoms may have continued with their menopausal therapy for longer than other women.”

Concerns about the risk of dementia with MHT date back to 2003 when data from the Women’s Health Initiative Memory Study showed that incidence of all-cause dementia doubled in women age 65 years and older after treatment with conjugated equine estrogens and medroxyprogesterone acetate for an average of 4 years. More recently, Finnish research has yielded conflicting data about risks.

The study

The investigators used two U.K. primary care databases (QResearch and CPRD) to analyze MHT prescriptions for 118,501 women age 55 and older diagnosed with dementia between 1998 and 2020 and 497,416 female controls matched by age and general practice, but with no record of dementia.

The cohort was older: mean age of cases was 83.5 years and mean duration of treatment was 16 years for an average age of 67.7 at first captured prescription, considerably later than when most women begin MHT. Relevant factors such as family history, smoking, alcohol consumption, preexisting conditions, and other prescribed drugs were taken into account.

Overall, 16,291 (14%) dementia cases and 68,726 (14%) controls had been exposed to MHT in the period up to 3 years before diagnosis.

After adjusting for potentially confounding factors, the researchers found no overall associations between hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment. Within the subgroup of women younger than 80 years who had been taking estrogen-only therapy for 10 years or more, a slightly decreased risk of dementia emerged: odds ratio, 0.85; 95% confidence interval, 0.76-0.94.

However, an analysis of dementia cases with a diagnosis specifically of Alzheimer’s disease showed a slight increase in risk associated with estrogen-progestin therapy. Increased risks of developing specifically Alzheimer’s disease emerged in those who had used combination therapy for 5-9 years (OR, 1.11; 95% CI, 1.04-1.20) and also for 10 years or more (OR, 1.19; 95% CI, 1.06-1.33). This risk rose gradually with each year of exposure, reaching an average 11% increased risk for use from 5-9 years and an average 19% for use 10 years or more – equivalent to, respectively, five and seven extra cases per 10,000 woman-years.

According to Jill M. Rabin, MD, a professor at the Feinstein Institutes for Medical Research and an ob.gyn. with Northwell Health in Manhasset, N.Y., the findings make sense for two reasons. “First, there are other health issues noted in women taking long-term combination hormonal therapy such as an increased risk of breast cancer,” she said in an interview. “Second, progesterone is recommended for women who have retained their uterus in order to counteract the potential effects of estrogen on the uterine lining causing possible overgrowth. There are systemic effects however of progesterone, as it counteracts estrogen, potentially decreasing its benefit on the neurological system.”

She added that this analysis is synchronous with other biological studies demonstrating possible neuroprotective effects of estrogen on the brain, especially among younger women. “The vascular system in the newly menopausal female is noted to have less endothelial and intimal thickening, better blood flow and oxygenation, and in general less vascular damage. Estrogen in these relatively younger, newly menopausal women may help to stabilize the vasculature as well as the neurologic system. On the other hand, estrogen therapy over the age of 80 may be delivered to a neurovasculature damaged with age and time, may be somewhat less beneficial.” Older women also have fewer estrogen receptors and, in general, other medical comorbidities.

According to the authors, the findings will be helpful to policy-makers, doctors, and patients when making choices about hormone therapy.

In an accompanying editorial, two U.S. researchers called the findings reassuring. Pauline M. Maki, PhD, of the University of Illinois at Chicago, and JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health in Boston, however, pointed out that the current study with its older cohort and older age at MHT initiation could not address the important issue of the “timing hypothesis” – namely, that earlier initiation of hormone therapy might confer greater protection against Alzheimer’s disease, compared with later use.

And while the current observations do not change the recommendation that MHT should not be used to prevent dementia, they are helpful for providers to put dementia findings in context for patients. “The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they wrote.

This study was funded by the U.K. National Institute for Health Research School for Primary Care Research.

Coauthor Dr. Julia Hippisley-Cox is a director of QResearch, EMIS Health, which supplies the QResearch database used for this work, and is a founder and shareholder of ClinRisk., which produces software to implement clinical risk algorithms.

For primary care patients feeling well enough to discontinue antidepressant medication, there was a higher rate of depressive relapse among those who discontinued therapy, compared with those who did not, a new study shows.

The results of the Antidepressants to Prevent Relapse in Depression (ANTLER) trial also suggest that “many patients can discontinue their antidepressants safely in primary care without relapsing, when there is a tapering regime,” said lead investigator Gemma Lewis, PhD, from University College London, in an interview.

The multicenter, randomized, double-blind trial, which was published in the New England Journal of Medicine (2021;385:1257-67), included 478 patients, from 150 primary care practices in the United Kingdom.

The participants (73% female, average age 54 years) had a history of at least two depressive episodes or had been taking antidepressants (citalopram, fluoxetine, sertraline, or mirtazapine) for at least 2 years. The vast majority of patients – 70% – had been using the drugs for more than 3 years, the researchers wrote.

Study participants were randomized to either maintain their antidepressant regimen or to taper off for up to 2 months before switching to a placebo.

Over a follow-up of 52 weeks, relapse occurred in 56% of those who discontinued, compared with 39% of those who maintained their regimen (hazard ratio, 2.06; P < .001). Relapse also occurred sooner in the discontinuation group (13 weeks vs. 19 weeks).

The definition of relapse was answering yes to either of the following two questions:

• Have you had a spell of feeling sad, miserable, or depressed?
• Have you been unable to enjoy or take an interest in things as much as you usually do?

Patients also had to report that one of these experiences had lasted for 2 weeks or more, and having had at least one of the following symptoms: depressive thoughts, fatigue, loss of concentration, or sleep disturbance.

By the end of the trial, 39% of patients in the group who discontinued taking an antidepressant had returned to taking that type of drug.

“We found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, we also found that 44% of those who discontinued their antidepressants did not relapse after a full year,” Dr. Lewis said.

Who can stop medications without relapsing is unknown

“Many people can stop their medication without relapsing, though at present we cannot identify who those people are,” noted Dr. Lewis.

“Our study did not investigate who is at higher risk of relapse … but this is something we will focus on in the future,” she said.

For primary care clinicians whose patients are considering discontinuation of antidepressant medication, “current best practice is to engage with patients’ priorities and collaborate in coming to a decision,” she noted.

“For the individual patient, it is only possible to know about the average likelihood of relapse – and the severity of potential relapses will also be unpredictable. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants to inform shared decision-making in primary care.”

Findings are ‘important’ but ‘disappointing’

In an editorial published alongside the study (N Engl J Med. 2021;385:1327-8), Jeffrey L. Jackson, MD, MPH, from the Zablocki VA Medical Center and the Medical College of Wisconsin in Milwaukee characterized the findings as “important but disappointing.”

“They confirm what most primary care physicians already knew or intuited. The frequency of relapse after the discontinuation of treatment is high, particularly among patients with several previous depressive episodes,” he explained.

Dr. Jackson also pointed out some unknowns about the trial, including the length trial participants had been in remission for depression.

“It is unclear whether the trial results are generalizable to primary care patients with a first episode of depression,” he said, and noted that participants with three or more previous depressive episodes were more than twice as likely to relapse, compared with participants with fewer episodes.

“I encourage patients with a single bout of depression, especially episodes that are triggered by a life event, such as loss of a loved one, to consider weaning antidepressant treatment after at least 6 months of remission,” he wrote. “For those with three or more previous bouts of depression, my practice has been to recommend that they anticipate medical treatment for life or, if they wish to stop taking medication, explore nonpharmacologic approaches, such as cognitive-behavior therapy.”

Protective effect of antidepressants was clear

“This is an important paper providing an evidence base to the often-cited recommendation that after two or more episodes of depression, antidepressant medication should be continued indefinitely,” said Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, who was not involved in the study.

“The protective effect of antidepressant medication here was clear – those who discontinued antidepressant medication had a clinically and significantly higher rate of relapse at the end of a year.”

Side effects can be significant

“It is important to note, though, that in the discontinuation group, 44% of patients did not experience a relapse,” Dr. Skolnik said. “While antidepressants work without significant side effects for many patients, for others there are significant side effects that include adverse sexual side effects, effects on appetite and weight, nighttime sweats, and other side effects.”

“So, this study should not be confused to mean that all patients who have had recurrent depression should remain on antidepressants long term. The decision about whether to continue an antidepressant is influenced by many things and should be a shared decision-making process between clinician and patient, informed by the important results of this study, the current situation of the patient, and most importantly, the patient’s informed decision of what they would like to do,” he said.

The study was funded by the U.K. National Institute for Health Research

Dr. Lewis, Dr. Jackson, and Dr. Skolnik reported no conflicts of interest.

For primary care patients feeling well enough to discontinue antidepressant medication, there was a higher rate of depressive relapse among those who discontinued therapy, compared with those who did not, a new study shows.

The results of the Antidepressants to Prevent Relapse in Depression (ANTLER) trial also suggest that “many patients can discontinue their antidepressants safely in primary care without relapsing, when there is a tapering regime,” said lead investigator Gemma Lewis, PhD, from University College London, in an interview.

The multicenter, randomized, double-blind trial, which was published in the New England Journal of Medicine (2021;385:1257-67), included 478 patients, from 150 primary care practices in the United Kingdom.

The participants (73% female, average age 54 years) had a history of at least two depressive episodes or had been taking antidepressants (citalopram, fluoxetine, sertraline, or mirtazapine) for at least 2 years. The vast majority of patients – 70% – had been using the drugs for more than 3 years, the researchers wrote.

Study participants were randomized to either maintain their antidepressant regimen or to taper off for up to 2 months before switching to a placebo.

Over a follow-up of 52 weeks, relapse occurred in 56% of those who discontinued, compared with 39% of those who maintained their regimen (hazard ratio, 2.06; P < .001). Relapse also occurred sooner in the discontinuation group (13 weeks vs. 19 weeks).

The definition of relapse was answering yes to either of the following two questions:

• Have you had a spell of feeling sad, miserable, or depressed?
• Have you been unable to enjoy or take an interest in things as much as you usually do?

Patients also had to report that one of these experiences had lasted for 2 weeks or more, and having had at least one of the following symptoms: depressive thoughts, fatigue, loss of concentration, or sleep disturbance.

By the end of the trial, 39% of patients in the group who discontinued taking an antidepressant had returned to taking that type of drug.

“We found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, we also found that 44% of those who discontinued their antidepressants did not relapse after a full year,” Dr. Lewis said.

Who can stop medications without relapsing is unknown

“Many people can stop their medication without relapsing, though at present we cannot identify who those people are,” noted Dr. Lewis.

“Our study did not investigate who is at higher risk of relapse … but this is something we will focus on in the future,” she said.

For primary care clinicians whose patients are considering discontinuation of antidepressant medication, “current best practice is to engage with patients’ priorities and collaborate in coming to a decision,” she noted.

“For the individual patient, it is only possible to know about the average likelihood of relapse – and the severity of potential relapses will also be unpredictable. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants to inform shared decision-making in primary care.”

Findings are ‘important’ but ‘disappointing’

In an editorial published alongside the study (N Engl J Med. 2021;385:1327-8), Jeffrey L. Jackson, MD, MPH, from the Zablocki VA Medical Center and the Medical College of Wisconsin in Milwaukee characterized the findings as “important but disappointing.”

“They confirm what most primary care physicians already knew or intuited. The frequency of relapse after the discontinuation of treatment is high, particularly among patients with several previous depressive episodes,” he explained.

Dr. Jackson also pointed out some unknowns about the trial, including the length trial participants had been in remission for depression.

“It is unclear whether the trial results are generalizable to primary care patients with a first episode of depression,” he said, and noted that participants with three or more previous depressive episodes were more than twice as likely to relapse, compared with participants with fewer episodes.

“I encourage patients with a single bout of depression, especially episodes that are triggered by a life event, such as loss of a loved one, to consider weaning antidepressant treatment after at least 6 months of remission,” he wrote. “For those with three or more previous bouts of depression, my practice has been to recommend that they anticipate medical treatment for life or, if they wish to stop taking medication, explore nonpharmacologic approaches, such as cognitive-behavior therapy.”

Protective effect of antidepressants was clear

“This is an important paper providing an evidence base to the often-cited recommendation that after two or more episodes of depression, antidepressant medication should be continued indefinitely,” said Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, who was not involved in the study.

“The protective effect of antidepressant medication here was clear – those who discontinued antidepressant medication had a clinically and significantly higher rate of relapse at the end of a year.”

Side effects can be significant

“It is important to note, though, that in the discontinuation group, 44% of patients did not experience a relapse,” Dr. Skolnik said. “While antidepressants work without significant side effects for many patients, for others there are significant side effects that include adverse sexual side effects, effects on appetite and weight, nighttime sweats, and other side effects.”

“So, this study should not be confused to mean that all patients who have had recurrent depression should remain on antidepressants long term. The decision about whether to continue an antidepressant is influenced by many things and should be a shared decision-making process between clinician and patient, informed by the important results of this study, the current situation of the patient, and most importantly, the patient’s informed decision of what they would like to do,” he said.

The study was funded by the U.K. National Institute for Health Research

Dr. Lewis, Dr. Jackson, and Dr. Skolnik reported no conflicts of interest.

For primary care patients feeling well enough to discontinue antidepressant medication, there was a higher rate of depressive relapse among those who discontinued therapy, compared with those who did not, a new study shows.

The results of the Antidepressants to Prevent Relapse in Depression (ANTLER) trial also suggest that “many patients can discontinue their antidepressants safely in primary care without relapsing, when there is a tapering regime,” said lead investigator Gemma Lewis, PhD, from University College London, in an interview.

The multicenter, randomized, double-blind trial, which was published in the New England Journal of Medicine (2021;385:1257-67), included 478 patients, from 150 primary care practices in the United Kingdom.

The participants (73% female, average age 54 years) had a history of at least two depressive episodes or had been taking antidepressants (citalopram, fluoxetine, sertraline, or mirtazapine) for at least 2 years. The vast majority of patients – 70% – had been using the drugs for more than 3 years, the researchers wrote.

Study participants were randomized to either maintain their antidepressant regimen or to taper off for up to 2 months before switching to a placebo.

Over a follow-up of 52 weeks, relapse occurred in 56% of those who discontinued, compared with 39% of those who maintained their regimen (hazard ratio, 2.06; P < .001). Relapse also occurred sooner in the discontinuation group (13 weeks vs. 19 weeks).

The definition of relapse was answering yes to either of the following two questions:

• Have you had a spell of feeling sad, miserable, or depressed?
• Have you been unable to enjoy or take an interest in things as much as you usually do?

Patients also had to report that one of these experiences had lasted for 2 weeks or more, and having had at least one of the following symptoms: depressive thoughts, fatigue, loss of concentration, or sleep disturbance.

By the end of the trial, 39% of patients in the group who discontinued taking an antidepressant had returned to taking that type of drug.

“We found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, we also found that 44% of those who discontinued their antidepressants did not relapse after a full year,” Dr. Lewis said.

Who can stop medications without relapsing is unknown

“Many people can stop their medication without relapsing, though at present we cannot identify who those people are,” noted Dr. Lewis.

“Our study did not investigate who is at higher risk of relapse … but this is something we will focus on in the future,” she said.

For primary care clinicians whose patients are considering discontinuation of antidepressant medication, “current best practice is to engage with patients’ priorities and collaborate in coming to a decision,” she noted.

“For the individual patient, it is only possible to know about the average likelihood of relapse – and the severity of potential relapses will also be unpredictable. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants to inform shared decision-making in primary care.”

Findings are ‘important’ but ‘disappointing’

In an editorial published alongside the study (N Engl J Med. 2021;385:1327-8), Jeffrey L. Jackson, MD, MPH, from the Zablocki VA Medical Center and the Medical College of Wisconsin in Milwaukee characterized the findings as “important but disappointing.”

“They confirm what most primary care physicians already knew or intuited. The frequency of relapse after the discontinuation of treatment is high, particularly among patients with several previous depressive episodes,” he explained.

Dr. Jackson also pointed out some unknowns about the trial, including the length trial participants had been in remission for depression.

“It is unclear whether the trial results are generalizable to primary care patients with a first episode of depression,” he said, and noted that participants with three or more previous depressive episodes were more than twice as likely to relapse, compared with participants with fewer episodes.

“I encourage patients with a single bout of depression, especially episodes that are triggered by a life event, such as loss of a loved one, to consider weaning antidepressant treatment after at least 6 months of remission,” he wrote. “For those with three or more previous bouts of depression, my practice has been to recommend that they anticipate medical treatment for life or, if they wish to stop taking medication, explore nonpharmacologic approaches, such as cognitive-behavior therapy.”

Protective effect of antidepressants was clear

“This is an important paper providing an evidence base to the often-cited recommendation that after two or more episodes of depression, antidepressant medication should be continued indefinitely,” said Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, who was not involved in the study.

“The protective effect of antidepressant medication here was clear – those who discontinued antidepressant medication had a clinically and significantly higher rate of relapse at the end of a year.”

Side effects can be significant

“It is important to note, though, that in the discontinuation group, 44% of patients did not experience a relapse,” Dr. Skolnik said. “While antidepressants work without significant side effects for many patients, for others there are significant side effects that include adverse sexual side effects, effects on appetite and weight, nighttime sweats, and other side effects.”

“So, this study should not be confused to mean that all patients who have had recurrent depression should remain on antidepressants long term. The decision about whether to continue an antidepressant is influenced by many things and should be a shared decision-making process between clinician and patient, informed by the important results of this study, the current situation of the patient, and most importantly, the patient’s informed decision of what they would like to do,” he said.

The study was funded by the U.K. National Institute for Health Research

Dr. Lewis, Dr. Jackson, and Dr. Skolnik reported no conflicts of interest.

Women with a history of migraine are more likely to experience severe or very severe hot flashes than women without migraines, according to research presented Sept. 24 at the hybrid annual meeting of the North American Menopause Society. An estimated one in five women experience migraine, and women tend to have greater migraine symptoms and disability, the authors note in their background information. Since migraines are also linked to a higher risk of cardiovascular disease, the authors sought to learn whether migraines were associated with vasomotor symptoms, another cardiovascular risk factor.

“The question in my mind is, can we do better at predicting cardiovascular risk in women because the risk prediction models that we have really don’t work all that well in women because they were designed for use in men,” Stephanie S. Faubion, MD, MBA, Penny and Bill George Director for Mayo Clinic’s Center for Women’s Health said in an interview. “My ultimate goal is to see if we can somehow use big data, artificial intelligence to figure out how to weight some of these female-specific or female-predominant factors to come up with a better model for cardiovascular risk prediction.”

The researchers analyzed cross-sectional data from 3,308 women who participated in the Data Registry on the Experiences of Aging, Menopause and Sexuality (DREAMS) study through Mayo Clinic sites in Rochester, Minn.; Scottsdale, Ariz.; and Jacksonville, Fla.. The women ranged in age from 45 to 60 years old, with an average age of 53, and the vast majority of them were white (95%) and had at least some college (93%). Most were also in a long-term relationship (85%), and a majority were employed (69%) and postmenopausal (67%).

The data, collected between May 2015 and December 2019, included a self-reported history of migraine and questionnaires that included the Menopause Rating Scale of menopause-related symptoms.

The researchers adjusted their findings to account for body mass index (BMI), menopause status, smoking status, depression, anxiety, current use of hormone therapy, and presence of low back pain within the past year. ”The diagnosis of low back pain, another pain disorder, was used to test the specificity of the association of migraine and vasomotor symptoms,” the authors write.

Just over a quarter of the women (27%) reported a history of migraine, and these women’s Menopause Rating Scale scores were an average 1.36 points greater than women without a history of migraines (P < .001). Women with self-reported migraine were also 40% more likely than women without migraines to report severe or very severe flashes versus reporting no hot flashes at all (odds ratio, 1.4; P = .02).

“The odds of reporting more severe hot flashes increased monotonically in women with a history of migraine,” the authors report. “In addition, women with low back pain had higher Menopause Rating Scale scores, but were no more likely to have severe/very severe hot flashes than those without back pain, confirming the specificity of the link between vasomotor symptoms and migraine.”

It’s not clear if migraine or hot flashes are risk factors that add to a woman’s existing cardiovascular risk profile or whether they are simply biomarkers of a shared pathway, Dr Faubion said in an interview. She speculates that the common link between migraine and vasomotor symptoms could be neurovascular dysregulation.

Rachael B. Smith, DO, of the department of ob.gyn. at the University of Arizona, Phoenix, was not involved in the research but found that hypothesis plausible as well.

“Our neurologic and vascular systems are coordinated physiologic processes working together for basic brain and body function,” Dr. Smith said in an interview. Some of the symptoms of migraines and menopause are similar and both are often explained by the dysfunction of these systems. The association between history of migraines and severity of vasomotor symptoms is very likely to be explained by this dysregulation between the neurologic and vascular systems.”

Dr. Smith also pointed out, however, that the largely homogeneous study population, all from the same national clinic system, makes it difficult to know how generalizable these findings are.

The primary clinical implications of these findings are that women’s providers need to be sure they’re asking their patients about migraine history and symptoms.

“The counseling we provide on menopausal symptoms should be better tailored to our patients’ medical history, specifically inquiring about history of migraines and how this may impact their symptoms,” Dr. Smith said.

The research was funded by the National Institutes of Health. Dr. Faubion and Dr. Smith had no disclosures.

Women with a history of migraine are more likely to experience severe or very severe hot flashes than women without migraines, according to research presented Sept. 24 at the hybrid annual meeting of the North American Menopause Society. An estimated one in five women experience migraine, and women tend to have greater migraine symptoms and disability, the authors note in their background information. Since migraines are also linked to a higher risk of cardiovascular disease, the authors sought to learn whether migraines were associated with vasomotor symptoms, another cardiovascular risk factor.

“The question in my mind is, can we do better at predicting cardiovascular risk in women because the risk prediction models that we have really don’t work all that well in women because they were designed for use in men,” Stephanie S. Faubion, MD, MBA, Penny and Bill George Director for Mayo Clinic’s Center for Women’s Health said in an interview. “My ultimate goal is to see if we can somehow use big data, artificial intelligence to figure out how to weight some of these female-specific or female-predominant factors to come up with a better model for cardiovascular risk prediction.”

The researchers analyzed cross-sectional data from 3,308 women who participated in the Data Registry on the Experiences of Aging, Menopause and Sexuality (DREAMS) study through Mayo Clinic sites in Rochester, Minn.; Scottsdale, Ariz.; and Jacksonville, Fla.. The women ranged in age from 45 to 60 years old, with an average age of 53, and the vast majority of them were white (95%) and had at least some college (93%). Most were also in a long-term relationship (85%), and a majority were employed (69%) and postmenopausal (67%).

The data, collected between May 2015 and December 2019, included a self-reported history of migraine and questionnaires that included the Menopause Rating Scale of menopause-related symptoms.

The researchers adjusted their findings to account for body mass index (BMI), menopause status, smoking status, depression, anxiety, current use of hormone therapy, and presence of low back pain within the past year. ”The diagnosis of low back pain, another pain disorder, was used to test the specificity of the association of migraine and vasomotor symptoms,” the authors write.

Just over a quarter of the women (27%) reported a history of migraine, and these women’s Menopause Rating Scale scores were an average 1.36 points greater than women without a history of migraines (P < .001). Women with self-reported migraine were also 40% more likely than women without migraines to report severe or very severe flashes versus reporting no hot flashes at all (odds ratio, 1.4; P = .02).

“The odds of reporting more severe hot flashes increased monotonically in women with a history of migraine,” the authors report. “In addition, women with low back pain had higher Menopause Rating Scale scores, but were no more likely to have severe/very severe hot flashes than those without back pain, confirming the specificity of the link between vasomotor symptoms and migraine.”

It’s not clear if migraine or hot flashes are risk factors that add to a woman’s existing cardiovascular risk profile or whether they are simply biomarkers of a shared pathway, Dr Faubion said in an interview. She speculates that the common link between migraine and vasomotor symptoms could be neurovascular dysregulation.

Rachael B. Smith, DO, of the department of ob.gyn. at the University of Arizona, Phoenix, was not involved in the research but found that hypothesis plausible as well.

“Our neurologic and vascular systems are coordinated physiologic processes working together for basic brain and body function,” Dr. Smith said in an interview. Some of the symptoms of migraines and menopause are similar and both are often explained by the dysfunction of these systems. The association between history of migraines and severity of vasomotor symptoms is very likely to be explained by this dysregulation between the neurologic and vascular systems.”

Dr. Smith also pointed out, however, that the largely homogeneous study population, all from the same national clinic system, makes it difficult to know how generalizable these findings are.

The primary clinical implications of these findings are that women’s providers need to be sure they’re asking their patients about migraine history and symptoms.

“The counseling we provide on menopausal symptoms should be better tailored to our patients’ medical history, specifically inquiring about history of migraines and how this may impact their symptoms,” Dr. Smith said.

The research was funded by the National Institutes of Health. Dr. Faubion and Dr. Smith had no disclosures.

Women with a history of migraine are more likely to experience severe or very severe hot flashes than women without migraines, according to research presented Sept. 24 at the hybrid annual meeting of the North American Menopause Society. An estimated one in five women experience migraine, and women tend to have greater migraine symptoms and disability, the authors note in their background information. Since migraines are also linked to a higher risk of cardiovascular disease, the authors sought to learn whether migraines were associated with vasomotor symptoms, another cardiovascular risk factor.

“The question in my mind is, can we do better at predicting cardiovascular risk in women because the risk prediction models that we have really don’t work all that well in women because they were designed for use in men,” Stephanie S. Faubion, MD, MBA, Penny and Bill George Director for Mayo Clinic’s Center for Women’s Health said in an interview. “My ultimate goal is to see if we can somehow use big data, artificial intelligence to figure out how to weight some of these female-specific or female-predominant factors to come up with a better model for cardiovascular risk prediction.”

The researchers analyzed cross-sectional data from 3,308 women who participated in the Data Registry on the Experiences of Aging, Menopause and Sexuality (DREAMS) study through Mayo Clinic sites in Rochester, Minn.; Scottsdale, Ariz.; and Jacksonville, Fla.. The women ranged in age from 45 to 60 years old, with an average age of 53, and the vast majority of them were white (95%) and had at least some college (93%). Most were also in a long-term relationship (85%), and a majority were employed (69%) and postmenopausal (67%).

The data, collected between May 2015 and December 2019, included a self-reported history of migraine and questionnaires that included the Menopause Rating Scale of menopause-related symptoms.

The researchers adjusted their findings to account for body mass index (BMI), menopause status, smoking status, depression, anxiety, current use of hormone therapy, and presence of low back pain within the past year. ”The diagnosis of low back pain, another pain disorder, was used to test the specificity of the association of migraine and vasomotor symptoms,” the authors write.

Just over a quarter of the women (27%) reported a history of migraine, and these women’s Menopause Rating Scale scores were an average 1.36 points greater than women without a history of migraines (P < .001). Women with self-reported migraine were also 40% more likely than women without migraines to report severe or very severe flashes versus reporting no hot flashes at all (odds ratio, 1.4; P = .02).

“The odds of reporting more severe hot flashes increased monotonically in women with a history of migraine,” the authors report. “In addition, women with low back pain had higher Menopause Rating Scale scores, but were no more likely to have severe/very severe hot flashes than those without back pain, confirming the specificity of the link between vasomotor symptoms and migraine.”

It’s not clear if migraine or hot flashes are risk factors that add to a woman’s existing cardiovascular risk profile or whether they are simply biomarkers of a shared pathway, Dr Faubion said in an interview. She speculates that the common link between migraine and vasomotor symptoms could be neurovascular dysregulation.

Rachael B. Smith, DO, of the department of ob.gyn. at the University of Arizona, Phoenix, was not involved in the research but found that hypothesis plausible as well.

“Our neurologic and vascular systems are coordinated physiologic processes working together for basic brain and body function,” Dr. Smith said in an interview. Some of the symptoms of migraines and menopause are similar and both are often explained by the dysfunction of these systems. The association between history of migraines and severity of vasomotor symptoms is very likely to be explained by this dysregulation between the neurologic and vascular systems.”

Dr. Smith also pointed out, however, that the largely homogeneous study population, all from the same national clinic system, makes it difficult to know how generalizable these findings are.

The primary clinical implications of these findings are that women’s providers need to be sure they’re asking their patients about migraine history and symptoms.

“The counseling we provide on menopausal symptoms should be better tailored to our patients’ medical history, specifically inquiring about history of migraines and how this may impact their symptoms,” Dr. Smith said.

The research was funded by the National Institutes of Health. Dr. Faubion and Dr. Smith had no disclosures.

The use of patient portals that provide access to electronic health records has dramatically increased in the past several years, and patients whose health care practitioner encouraged them to use their online portal accessed them at a higher rate than those who were not encouraged to do so.

These were among the top-line results of a national survey of U.S. adults conducted by the National Institutes of Health from January 2020 to April 2020. Although the COVID-19 pandemic hit the United States in the middle of that period, a report on the survey by the Office of the National Coordinator for Health IT stated, “These findings largely reflect prepandemic rates of individuals being offered and subsequently using their online medical record, also known as a patient portal.”

But with more patient access can come additional work for physicians and other health care practitioners, ranging from an onslaught of patient communications to managing data sent to them by patients.

According to the report, 59% of individuals were offered access to their patient portal, and 38% accessed their record at least once in 2020. By comparison, in 2014, just 42% were offered access to their portal, and 25% used it. But these percentages hardly changed from 2019 to 2020.

The increase in the percentage of people who accessed portals reflects the fact that more people were offered access. In addition, there were signs of rising activity among portal users.

Among patients offered access to their patient portal, 64% accessed it at least once in 2020 – 11 percentage points more than in 2017. Twenty-seven percent of those who had access to a portal used it once or twice; 20% accessed it three to five times; and 18% used it six or more times. The latter two percentages were significantly higher than in 2017.

Of the respondents who were offered access to portals but didn’t use them, 69% said they didn’t access the portal because they preferred to speak with their health care practitioner directly. Sixty-three percent said they didn’t see a need to use their online medical record. This was similar to the percentage 3 years earlier. Other reasons included respondents’ concerns about the privacy/security of online medical records (24%), their lack of comfort with computers (20%), and their lack of Internet access (13%).
 

The pros and cons of patient portals, greater access

Among portal users who accessed their records through a mobile health app, 51% used the app to facilitate discussions with their health care practitioner in 2020, an 8–percentage point increase from 2017. Fifty-percent of the mobile health app users utilized it to make a decision about how to treat an illness or condition, up from 45% in 2017. And 71% of these individuals used their app to track progress on a health-related goal, just a bit more than in 2017.

Individuals who were encouraged by their health care practitioner to use their patient portal viewed clinical notes and exchanged secure messages with their practitioner at higher rates than those who had not been encouraged. This is not surprising, but it reflects an unintended result of patient portals that many physicians have found burdensome, especially during the pandemic: overflowing electronic in-boxes.

Robert Wachter, MD, chairman of the department of medicine at the University of California, San Francisco, recently tweeted, “We’re seeing huge uptick in in-box messages for MDs during COVID – now seems like biggest driver of MD burnout. The fundamental problem: We turned on 24/7/365 access for patients (who of course like it) with no operational or business model to handle it. Crucial that we fix this.”

Steven Waldren, MD, vice president and chief medical informatics officer at the American Academy of Family Physicians, told this news organization that he agrees that this is a major challenge. “In-box management is a burden on physicians and practices,” he said. “However, it can be done better, either through a team in-box or through better use of technology.”

The team in-box he refers to is a mechanism for triaging patient messages. For example, a triage nurse can look at the messages and decide which ones can be handled by staff and which ones the doctor needs to see. Or physicians and front office staff can see the messages at the same time; a nurse can triage some messages according to protocols, and the physician can respond to any message, depending on what he or she knows about the patient.

Technology can also be enlisted in the effort, he suggested, perhaps by automating the triaging of messages such as prescription refill requests or using artificial intelligence to sort messages by content.

Making patient records portable

Nearly 40% of portal users accessed it using a smartphone app (17%) or with both their smartphone app and their computer (22%). Sixty-one percent of users relied exclusively on computers to access their portals.

About a third of patient portal users downloaded their online medical records in 2020. This proportion has nearly doubled from 17% since 2017, the ONC report noted.

Although the survey didn’t ask about multiple downloads, it appears that most people had to download their records separately from the patient portal of each practitioner who cared for them. Although the Apple Health app allows people to download records to their iPhones from multiple portals using a standard application programming interface, the ONC report says that only 5% of respondents transmitted their records to a service or app, up slightly from 3% in 2017.

Dr. Waldren hopes most patients will have the ability to download and integrate records from multiple practitioners in a few years, but he wouldn’t bet on it.

“A fair amount of work needs to be done on the business side and on figuring out how the data get connected together,” he said. “And there are still privacy concerns with apps.”

Overall, 21% of portal users transmitted their data to at least one outside party in 2020, compared with 14% in 2017. Seventeen percent of them sent their records to another health care practitioner, up from 10% in 2017. Five percent of the users transmitted their records to a caregiver, slightly more than in 2017.

Managing data is a challenge

Asked how physicians feel about portal users adding information to their record or correcting inaccurate information, Dr. Waldren says, “Doctors are already comfortable with patient-generated data. The challenge is managing it. If the patient provides data that’s not easy to put in the EHR, that’s going to add work, and they don’t want to see 100 blood pressure readings.

“You’d be hard-pressed to find a doctor who doesn’t welcome additional information about the patient’s health, but it can be onerous and can take time to enter the data,” Dr. Waldren said.

Overall, he said, “Giving patients the ability to take more ownership of their health and participate in their own care is good and can help us move forward. How this will be integrated into patient care is another question.”

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

The use of patient portals that provide access to electronic health records has dramatically increased in the past several years, and patients whose health care practitioner encouraged them to use their online portal accessed them at a higher rate than those who were not encouraged to do so.

These were among the top-line results of a national survey of U.S. adults conducted by the National Institutes of Health from January 2020 to April 2020. Although the COVID-19 pandemic hit the United States in the middle of that period, a report on the survey by the Office of the National Coordinator for Health IT stated, “These findings largely reflect prepandemic rates of individuals being offered and subsequently using their online medical record, also known as a patient portal.”

But with more patient access can come additional work for physicians and other health care practitioners, ranging from an onslaught of patient communications to managing data sent to them by patients.

According to the report, 59% of individuals were offered access to their patient portal, and 38% accessed their record at least once in 2020. By comparison, in 2014, just 42% were offered access to their portal, and 25% used it. But these percentages hardly changed from 2019 to 2020.

The increase in the percentage of people who accessed portals reflects the fact that more people were offered access. In addition, there were signs of rising activity among portal users.

Among patients offered access to their patient portal, 64% accessed it at least once in 2020 – 11 percentage points more than in 2017. Twenty-seven percent of those who had access to a portal used it once or twice; 20% accessed it three to five times; and 18% used it six or more times. The latter two percentages were significantly higher than in 2017.

Of the respondents who were offered access to portals but didn’t use them, 69% said they didn’t access the portal because they preferred to speak with their health care practitioner directly. Sixty-three percent said they didn’t see a need to use their online medical record. This was similar to the percentage 3 years earlier. Other reasons included respondents’ concerns about the privacy/security of online medical records (24%), their lack of comfort with computers (20%), and their lack of Internet access (13%).
 

The pros and cons of patient portals, greater access

Among portal users who accessed their records through a mobile health app, 51% used the app to facilitate discussions with their health care practitioner in 2020, an 8–percentage point increase from 2017. Fifty-percent of the mobile health app users utilized it to make a decision about how to treat an illness or condition, up from 45% in 2017. And 71% of these individuals used their app to track progress on a health-related goal, just a bit more than in 2017.

Individuals who were encouraged by their health care practitioner to use their patient portal viewed clinical notes and exchanged secure messages with their practitioner at higher rates than those who had not been encouraged. This is not surprising, but it reflects an unintended result of patient portals that many physicians have found burdensome, especially during the pandemic: overflowing electronic in-boxes.

Robert Wachter, MD, chairman of the department of medicine at the University of California, San Francisco, recently tweeted, “We’re seeing huge uptick in in-box messages for MDs during COVID – now seems like biggest driver of MD burnout. The fundamental problem: We turned on 24/7/365 access for patients (who of course like it) with no operational or business model to handle it. Crucial that we fix this.”

Steven Waldren, MD, vice president and chief medical informatics officer at the American Academy of Family Physicians, told this news organization that he agrees that this is a major challenge. “In-box management is a burden on physicians and practices,” he said. “However, it can be done better, either through a team in-box or through better use of technology.”

The team in-box he refers to is a mechanism for triaging patient messages. For example, a triage nurse can look at the messages and decide which ones can be handled by staff and which ones the doctor needs to see. Or physicians and front office staff can see the messages at the same time; a nurse can triage some messages according to protocols, and the physician can respond to any message, depending on what he or she knows about the patient.

Technology can also be enlisted in the effort, he suggested, perhaps by automating the triaging of messages such as prescription refill requests or using artificial intelligence to sort messages by content.

Making patient records portable

Nearly 40% of portal users accessed it using a smartphone app (17%) or with both their smartphone app and their computer (22%). Sixty-one percent of users relied exclusively on computers to access their portals.

About a third of patient portal users downloaded their online medical records in 2020. This proportion has nearly doubled from 17% since 2017, the ONC report noted.

Although the survey didn’t ask about multiple downloads, it appears that most people had to download their records separately from the patient portal of each practitioner who cared for them. Although the Apple Health app allows people to download records to their iPhones from multiple portals using a standard application programming interface, the ONC report says that only 5% of respondents transmitted their records to a service or app, up slightly from 3% in 2017.

Dr. Waldren hopes most patients will have the ability to download and integrate records from multiple practitioners in a few years, but he wouldn’t bet on it.

“A fair amount of work needs to be done on the business side and on figuring out how the data get connected together,” he said. “And there are still privacy concerns with apps.”

Overall, 21% of portal users transmitted their data to at least one outside party in 2020, compared with 14% in 2017. Seventeen percent of them sent their records to another health care practitioner, up from 10% in 2017. Five percent of the users transmitted their records to a caregiver, slightly more than in 2017.

Managing data is a challenge

Asked how physicians feel about portal users adding information to their record or correcting inaccurate information, Dr. Waldren says, “Doctors are already comfortable with patient-generated data. The challenge is managing it. If the patient provides data that’s not easy to put in the EHR, that’s going to add work, and they don’t want to see 100 blood pressure readings.

“You’d be hard-pressed to find a doctor who doesn’t welcome additional information about the patient’s health, but it can be onerous and can take time to enter the data,” Dr. Waldren said.

Overall, he said, “Giving patients the ability to take more ownership of their health and participate in their own care is good and can help us move forward. How this will be integrated into patient care is another question.”

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

The use of patient portals that provide access to electronic health records has dramatically increased in the past several years, and patients whose health care practitioner encouraged them to use their online portal accessed them at a higher rate than those who were not encouraged to do so.

These were among the top-line results of a national survey of U.S. adults conducted by the National Institutes of Health from January 2020 to April 2020. Although the COVID-19 pandemic hit the United States in the middle of that period, a report on the survey by the Office of the National Coordinator for Health IT stated, “These findings largely reflect prepandemic rates of individuals being offered and subsequently using their online medical record, also known as a patient portal.”

But with more patient access can come additional work for physicians and other health care practitioners, ranging from an onslaught of patient communications to managing data sent to them by patients.

According to the report, 59% of individuals were offered access to their patient portal, and 38% accessed their record at least once in 2020. By comparison, in 2014, just 42% were offered access to their portal, and 25% used it. But these percentages hardly changed from 2019 to 2020.

The increase in the percentage of people who accessed portals reflects the fact that more people were offered access. In addition, there were signs of rising activity among portal users.

Among patients offered access to their patient portal, 64% accessed it at least once in 2020 – 11 percentage points more than in 2017. Twenty-seven percent of those who had access to a portal used it once or twice; 20% accessed it three to five times; and 18% used it six or more times. The latter two percentages were significantly higher than in 2017.

Of the respondents who were offered access to portals but didn’t use them, 69% said they didn’t access the portal because they preferred to speak with their health care practitioner directly. Sixty-three percent said they didn’t see a need to use their online medical record. This was similar to the percentage 3 years earlier. Other reasons included respondents’ concerns about the privacy/security of online medical records (24%), their lack of comfort with computers (20%), and their lack of Internet access (13%).
 

The pros and cons of patient portals, greater access

Among portal users who accessed their records through a mobile health app, 51% used the app to facilitate discussions with their health care practitioner in 2020, an 8–percentage point increase from 2017. Fifty-percent of the mobile health app users utilized it to make a decision about how to treat an illness or condition, up from 45% in 2017. And 71% of these individuals used their app to track progress on a health-related goal, just a bit more than in 2017.

Individuals who were encouraged by their health care practitioner to use their patient portal viewed clinical notes and exchanged secure messages with their practitioner at higher rates than those who had not been encouraged. This is not surprising, but it reflects an unintended result of patient portals that many physicians have found burdensome, especially during the pandemic: overflowing electronic in-boxes.

Robert Wachter, MD, chairman of the department of medicine at the University of California, San Francisco, recently tweeted, “We’re seeing huge uptick in in-box messages for MDs during COVID – now seems like biggest driver of MD burnout. The fundamental problem: We turned on 24/7/365 access for patients (who of course like it) with no operational or business model to handle it. Crucial that we fix this.”

Steven Waldren, MD, vice president and chief medical informatics officer at the American Academy of Family Physicians, told this news organization that he agrees that this is a major challenge. “In-box management is a burden on physicians and practices,” he said. “However, it can be done better, either through a team in-box or through better use of technology.”

The team in-box he refers to is a mechanism for triaging patient messages. For example, a triage nurse can look at the messages and decide which ones can be handled by staff and which ones the doctor needs to see. Or physicians and front office staff can see the messages at the same time; a nurse can triage some messages according to protocols, and the physician can respond to any message, depending on what he or she knows about the patient.

Technology can also be enlisted in the effort, he suggested, perhaps by automating the triaging of messages such as prescription refill requests or using artificial intelligence to sort messages by content.

Making patient records portable

Nearly 40% of portal users accessed it using a smartphone app (17%) or with both their smartphone app and their computer (22%). Sixty-one percent of users relied exclusively on computers to access their portals.

About a third of patient portal users downloaded their online medical records in 2020. This proportion has nearly doubled from 17% since 2017, the ONC report noted.

Although the survey didn’t ask about multiple downloads, it appears that most people had to download their records separately from the patient portal of each practitioner who cared for them. Although the Apple Health app allows people to download records to their iPhones from multiple portals using a standard application programming interface, the ONC report says that only 5% of respondents transmitted their records to a service or app, up slightly from 3% in 2017.

Dr. Waldren hopes most patients will have the ability to download and integrate records from multiple practitioners in a few years, but he wouldn’t bet on it.

“A fair amount of work needs to be done on the business side and on figuring out how the data get connected together,” he said. “And there are still privacy concerns with apps.”

Overall, 21% of portal users transmitted their data to at least one outside party in 2020, compared with 14% in 2017. Seventeen percent of them sent their records to another health care practitioner, up from 10% in 2017. Five percent of the users transmitted their records to a caregiver, slightly more than in 2017.

Managing data is a challenge

Asked how physicians feel about portal users adding information to their record or correcting inaccurate information, Dr. Waldren says, “Doctors are already comfortable with patient-generated data. The challenge is managing it. If the patient provides data that’s not easy to put in the EHR, that’s going to add work, and they don’t want to see 100 blood pressure readings.

“You’d be hard-pressed to find a doctor who doesn’t welcome additional information about the patient’s health, but it can be onerous and can take time to enter the data,” Dr. Waldren said.

Overall, he said, “Giving patients the ability to take more ownership of their health and participate in their own care is good and can help us move forward. How this will be integrated into patient care is another question.”

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

Long-term survival outcomes are better when postmenopausal women are on an aromatase inhibitor for 5 years, instead of the usual 2-3 years, following tamoxifen for hormone receptor–positive breast cancer, according to a randomized, open-label trial from Italy with over 2,000 women.

The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.

Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.

The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.

Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.

Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).

Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).

At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.

It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.

With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.

Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.

For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.

However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.

Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.

There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”

The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.

[email protected]

Long-term survival outcomes are better when postmenopausal women are on an aromatase inhibitor for 5 years, instead of the usual 2-3 years, following tamoxifen for hormone receptor–positive breast cancer, according to a randomized, open-label trial from Italy with over 2,000 women.

The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.

Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.

The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.

Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.

Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).

Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).

At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.

It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.

With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.

Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.

For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.

However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.

Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.

There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”

The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.

[email protected]

Long-term survival outcomes are better when postmenopausal women are on an aromatase inhibitor for 5 years, instead of the usual 2-3 years, following tamoxifen for hormone receptor–positive breast cancer, according to a randomized, open-label trial from Italy with over 2,000 women.

The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.

Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.

The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.

Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.

Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).

Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).

At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.

It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.

With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.

Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.

For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.

However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.

Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.

There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”

The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.

[email protected]

After nearly a decade, the American Academy of Orthopaedic Surgeons has updated its guidance on nonoperative treatment for knee osteoarthritis.

The clinical practice guidelines, released Sept. 13, 2021, is the third edition of the orthopedic society’s clinical practice recommendations.

According to Robert Brophy, MD, FAAOS, an orthopedic surgeon at Washington University, St. Louis, and cochair of the AAOS clinical practice guideline work group, the AAOS guidelines are a “living document” that needs periodic updating as new research comes to light.

“The methodology for maintaining the AAOS guidelines aims to update guideline documents at least every 10 years,” Dr. Brophy said in an interview. “Since the last edition was from 2013, it was time to provide an updated guideline on this very important topic that affects such a high percentage of our patients and providers.”

The guidelines work group, composed of 12 medical doctors and 1 physical therapist, evaluated the evidence for 29 areas of treatment.

A rating scale based on available evidence and the strength of related medical studies labeled each treatment area as demonstrating strong, moderate, or limited evidence.

Eight treatment modalities weighed in with strong evidence for or against their use: lateral wedge insoles, topical or oral NSAIDs, exercise (supervised or unsupervised), self-management programs, patient education programs, oral acetaminophen, and oral opioids.

According to Dr. Brophy, many of the recommendations assigned a strong evidence base were similar to the prior edition of the guidelines.
 

Oral medications

NSAIDs and acetaminophen still remain steadfast options for the treatment of knee pain secondary to OA.

decade3d/Thinkstock

The most notable change was that opioids, which have a long history of being used to treat pain, are strongly recommended not to be used for arthritis.

“Reflecting the growing awareness of and emphasis on the opioid epidemic, one of the strongest changes between the current and prior guidelines centers on the use of opioid medications,” Dr. Brophy said. “In the prior guideline, a strong recommendation was made in favor of tramadol with an inconclusive recommendation made regarding other opioid medications. The updated guideline demonstrates clearly the evidence does not support the use of opioid medications – including tramadol – to treat knee osteoarthritis.”

This may require some education for both patients and doctors to buy in that knee pain can be treated adequately with NSAIDs and acetaminophen.

Patients may not understand that anti-inflammatory drugs treat the pain they are experiencing. They may equate an opioid with a “pain pill” and may need education from their doctor that NSAIDs and acetaminophen not only can relieve their pain, but also avoid potential adverse events prior to or after surgery should they progress to knee replacement surgery.

Furthermore, primary care physicians may not be looking at the long-term picture. Solving a short-term pain problem with opioids may limit the medication’s ability to provide pain relief after surgery should a patient develop a tolerance to the medication’s effects.
 

Recommendations on hip and foot alignment interventions

When it comes to alignment and joint stresses, the knee is sometimes considered the innocent bystander of hip and foot alignment.

Insoles. How the hip and foot align with each can determine the amount of weight that passes through the medial (inner) or lateral (outer) compartment of the knee. To that end, lateral foot insoles have been used in the past for unloading parts of the knee.

Nevertheless, recent evidence has failed to demonstrate a significant benefit for insoles in the setting of OA knee pain, earning the practice a strong recommendation against its use.

High-tibial osteotomy (HTO). The weight-bearing axis of the lower-extremity axis can also be realigned with HTO. The procedure shifts the body’s weight slightly to the opposite side of the knee.

Newer research has led the practice to be downgraded one level in the new guideline, from moderate to limited, despite its widespread use.

It will, however, likely continue to be used as an alternative to total knee replacement in younger patients and to shift weight away from an area of the knee where cartilage is being restored with a concomitant surgical procedure, according to the work group. They noted that additional research studies on the long-term efficacy of the procedure are still needed.

Topical treatments. The guideline authors gave these a strong recommendation. Gels with anti-inflammatory medication have long been available but were prescription only or of considerable cost. Now several affordable over-the-counter options with the same prescription strength can be found in pharmacies and supermarkets.

What makes these medications unique is that they have an NSAID medication in the formulation, which the vast majority of topical treatments found on shelves do not. They also benefit patients who are unable to tolerate oral NSAIDs because of gastrointestinal side effects.

Comparison with 2019 OARSI recommendations

In 2019, the Osteoarthritis Research Society International also published guidelines for the management of OA of the hand, hip, and knee.

Thomas Trojian, MD, a family medicine physician with expertise in sports medicine in York, Pa., and member of both the AAOS and OARSI recommendation committees, noted that the OARSI guidelines are meant to be practical guidelines of stepwise nonoperative treatment.

He said in an interview that “the OARSI guidelines recommend dietary weight management, education, and land-based [exercise] therapy, next topical NSAIDs, then injection therapy.”

Intra-articular steroids and viscosupplementation injection therapy in the form of hyaluronic acid derivatives continue to be a mainstay of treatment for both groups.

The AAOS group notably gave a moderate strength recommendation for intra-articular steroid injections with the caveat that the effects typically only last for 3 months. They also included newer extended-release steroid injections in the recommendation, stating that the evidence moderately suggests they provide more benefit than traditional short-acting steroid injections.
 

Methodology differs between guidelines

In the areas where the guidelines don’t fully line up, it is important to remember the methodology of each group often drives the guidelines and recommendations.

According to Yale Fillingham, MD, an orthopedic surgeon in group private practice in the greater Philadelphia area and the other cochair of the AAOS guidelines committee, the biggest difference between the AAOS and OARSI guidelines is that, although the OARSI guidelines are also grounded in the literature, the recommendation level was based on voting among panel members.

“The AAOS methodology requires the recommendation and strength of the recommendation to be dictated primarily by the best available evidence in the literature and much less on the expertise and opinion of the voting panel,” Dr. Fillingham said in an interview.

He pointed out that the AAOS voting panel can alter the guideline by adjusting the strength of the recommendation but noted it was only in very clearly defined situations. Therefore, the differences in methodology between the groups make it difficult to directly compare the two guidelines.

Multiple guidelines do, however, point to the importance of the issue. Dr. Fillingham commented: “The numerous organizations that have produced guidelines on the treatment of knee osteoarthritis are a testament to the widespread and profound impact of knee osteoarthritis on our health care system and society.”

As a member of both recommendation groups, Dr. Trojian finds both guidelines reveal the importance of understanding that knee OA is a chronic illness. “There are ways we can manage knee OA and reduce the morbidity. ... The core skills of motivational interviewing are important. Open-ended questions, affirmation, reflection, and summarizing are needed to help patients find and remove roadblocks to promote lifestyle changes.”

Dr. Brophy, Dr. Trojian, and Dr. Fillingham have disclosed no relevant financial relationships.

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

After nearly a decade, the American Academy of Orthopaedic Surgeons has updated its guidance on nonoperative treatment for knee osteoarthritis.

The clinical practice guidelines, released Sept. 13, 2021, is the third edition of the orthopedic society’s clinical practice recommendations.

According to Robert Brophy, MD, FAAOS, an orthopedic surgeon at Washington University, St. Louis, and cochair of the AAOS clinical practice guideline work group, the AAOS guidelines are a “living document” that needs periodic updating as new research comes to light.

“The methodology for maintaining the AAOS guidelines aims to update guideline documents at least every 10 years,” Dr. Brophy said in an interview. “Since the last edition was from 2013, it was time to provide an updated guideline on this very important topic that affects such a high percentage of our patients and providers.”

The guidelines work group, composed of 12 medical doctors and 1 physical therapist, evaluated the evidence for 29 areas of treatment.

A rating scale based on available evidence and the strength of related medical studies labeled each treatment area as demonstrating strong, moderate, or limited evidence.

Eight treatment modalities weighed in with strong evidence for or against their use: lateral wedge insoles, topical or oral NSAIDs, exercise (supervised or unsupervised), self-management programs, patient education programs, oral acetaminophen, and oral opioids.

According to Dr. Brophy, many of the recommendations assigned a strong evidence base were similar to the prior edition of the guidelines.
 

Oral medications

NSAIDs and acetaminophen still remain steadfast options for the treatment of knee pain secondary to OA.

decade3d/Thinkstock

The most notable change was that opioids, which have a long history of being used to treat pain, are strongly recommended not to be used for arthritis.

“Reflecting the growing awareness of and emphasis on the opioid epidemic, one of the strongest changes between the current and prior guidelines centers on the use of opioid medications,” Dr. Brophy said. “In the prior guideline, a strong recommendation was made in favor of tramadol with an inconclusive recommendation made regarding other opioid medications. The updated guideline demonstrates clearly the evidence does not support the use of opioid medications – including tramadol – to treat knee osteoarthritis.”

This may require some education for both patients and doctors to buy in that knee pain can be treated adequately with NSAIDs and acetaminophen.

Patients may not understand that anti-inflammatory drugs treat the pain they are experiencing. They may equate an opioid with a “pain pill” and may need education from their doctor that NSAIDs and acetaminophen not only can relieve their pain, but also avoid potential adverse events prior to or after surgery should they progress to knee replacement surgery.

Furthermore, primary care physicians may not be looking at the long-term picture. Solving a short-term pain problem with opioids may limit the medication’s ability to provide pain relief after surgery should a patient develop a tolerance to the medication’s effects.
 

Recommendations on hip and foot alignment interventions

When it comes to alignment and joint stresses, the knee is sometimes considered the innocent bystander of hip and foot alignment.

Insoles. How the hip and foot align with each can determine the amount of weight that passes through the medial (inner) or lateral (outer) compartment of the knee. To that end, lateral foot insoles have been used in the past for unloading parts of the knee.

Nevertheless, recent evidence has failed to demonstrate a significant benefit for insoles in the setting of OA knee pain, earning the practice a strong recommendation against its use.

High-tibial osteotomy (HTO). The weight-bearing axis of the lower-extremity axis can also be realigned with HTO. The procedure shifts the body’s weight slightly to the opposite side of the knee.

Newer research has led the practice to be downgraded one level in the new guideline, from moderate to limited, despite its widespread use.

It will, however, likely continue to be used as an alternative to total knee replacement in younger patients and to shift weight away from an area of the knee where cartilage is being restored with a concomitant surgical procedure, according to the work group. They noted that additional research studies on the long-term efficacy of the procedure are still needed.

Topical treatments. The guideline authors gave these a strong recommendation. Gels with anti-inflammatory medication have long been available but were prescription only or of considerable cost. Now several affordable over-the-counter options with the same prescription strength can be found in pharmacies and supermarkets.

What makes these medications unique is that they have an NSAID medication in the formulation, which the vast majority of topical treatments found on shelves do not. They also benefit patients who are unable to tolerate oral NSAIDs because of gastrointestinal side effects.

Comparison with 2019 OARSI recommendations

In 2019, the Osteoarthritis Research Society International also published guidelines for the management of OA of the hand, hip, and knee.

Thomas Trojian, MD, a family medicine physician with expertise in sports medicine in York, Pa., and member of both the AAOS and OARSI recommendation committees, noted that the OARSI guidelines are meant to be practical guidelines of stepwise nonoperative treatment.

He said in an interview that “the OARSI guidelines recommend dietary weight management, education, and land-based [exercise] therapy, next topical NSAIDs, then injection therapy.”

Intra-articular steroids and viscosupplementation injection therapy in the form of hyaluronic acid derivatives continue to be a mainstay of treatment for both groups.

The AAOS group notably gave a moderate strength recommendation for intra-articular steroid injections with the caveat that the effects typically only last for 3 months. They also included newer extended-release steroid injections in the recommendation, stating that the evidence moderately suggests they provide more benefit than traditional short-acting steroid injections.
 

Methodology differs between guidelines

In the areas where the guidelines don’t fully line up, it is important to remember the methodology of each group often drives the guidelines and recommendations.

According to Yale Fillingham, MD, an orthopedic surgeon in group private practice in the greater Philadelphia area and the other cochair of the AAOS guidelines committee, the biggest difference between the AAOS and OARSI guidelines is that, although the OARSI guidelines are also grounded in the literature, the recommendation level was based on voting among panel members.

“The AAOS methodology requires the recommendation and strength of the recommendation to be dictated primarily by the best available evidence in the literature and much less on the expertise and opinion of the voting panel,” Dr. Fillingham said in an interview.

He pointed out that the AAOS voting panel can alter the guideline by adjusting the strength of the recommendation but noted it was only in very clearly defined situations. Therefore, the differences in methodology between the groups make it difficult to directly compare the two guidelines.

Multiple guidelines do, however, point to the importance of the issue. Dr. Fillingham commented: “The numerous organizations that have produced guidelines on the treatment of knee osteoarthritis are a testament to the widespread and profound impact of knee osteoarthritis on our health care system and society.”

As a member of both recommendation groups, Dr. Trojian finds both guidelines reveal the importance of understanding that knee OA is a chronic illness. “There are ways we can manage knee OA and reduce the morbidity. ... The core skills of motivational interviewing are important. Open-ended questions, affirmation, reflection, and summarizing are needed to help patients find and remove roadblocks to promote lifestyle changes.”

Dr. Brophy, Dr. Trojian, and Dr. Fillingham have disclosed no relevant financial relationships.

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

After nearly a decade, the American Academy of Orthopaedic Surgeons has updated its guidance on nonoperative treatment for knee osteoarthritis.

The clinical practice guidelines, released Sept. 13, 2021, is the third edition of the orthopedic society’s clinical practice recommendations.

According to Robert Brophy, MD, FAAOS, an orthopedic surgeon at Washington University, St. Louis, and cochair of the AAOS clinical practice guideline work group, the AAOS guidelines are a “living document” that needs periodic updating as new research comes to light.

“The methodology for maintaining the AAOS guidelines aims to update guideline documents at least every 10 years,” Dr. Brophy said in an interview. “Since the last edition was from 2013, it was time to provide an updated guideline on this very important topic that affects such a high percentage of our patients and providers.”

The guidelines work group, composed of 12 medical doctors and 1 physical therapist, evaluated the evidence for 29 areas of treatment.

A rating scale based on available evidence and the strength of related medical studies labeled each treatment area as demonstrating strong, moderate, or limited evidence.

Eight treatment modalities weighed in with strong evidence for or against their use: lateral wedge insoles, topical or oral NSAIDs, exercise (supervised or unsupervised), self-management programs, patient education programs, oral acetaminophen, and oral opioids.

According to Dr. Brophy, many of the recommendations assigned a strong evidence base were similar to the prior edition of the guidelines.
 

Oral medications

NSAIDs and acetaminophen still remain steadfast options for the treatment of knee pain secondary to OA.

decade3d/Thinkstock

The most notable change was that opioids, which have a long history of being used to treat pain, are strongly recommended not to be used for arthritis.

“Reflecting the growing awareness of and emphasis on the opioid epidemic, one of the strongest changes between the current and prior guidelines centers on the use of opioid medications,” Dr. Brophy said. “In the prior guideline, a strong recommendation was made in favor of tramadol with an inconclusive recommendation made regarding other opioid medications. The updated guideline demonstrates clearly the evidence does not support the use of opioid medications – including tramadol – to treat knee osteoarthritis.”

This may require some education for both patients and doctors to buy in that knee pain can be treated adequately with NSAIDs and acetaminophen.

Patients may not understand that anti-inflammatory drugs treat the pain they are experiencing. They may equate an opioid with a “pain pill” and may need education from their doctor that NSAIDs and acetaminophen not only can relieve their pain, but also avoid potential adverse events prior to or after surgery should they progress to knee replacement surgery.

Furthermore, primary care physicians may not be looking at the long-term picture. Solving a short-term pain problem with opioids may limit the medication’s ability to provide pain relief after surgery should a patient develop a tolerance to the medication’s effects.
 

Recommendations on hip and foot alignment interventions

When it comes to alignment and joint stresses, the knee is sometimes considered the innocent bystander of hip and foot alignment.

Insoles. How the hip and foot align with each can determine the amount of weight that passes through the medial (inner) or lateral (outer) compartment of the knee. To that end, lateral foot insoles have been used in the past for unloading parts of the knee.

Nevertheless, recent evidence has failed to demonstrate a significant benefit for insoles in the setting of OA knee pain, earning the practice a strong recommendation against its use.

High-tibial osteotomy (HTO). The weight-bearing axis of the lower-extremity axis can also be realigned with HTO. The procedure shifts the body’s weight slightly to the opposite side of the knee.

Newer research has led the practice to be downgraded one level in the new guideline, from moderate to limited, despite its widespread use.

It will, however, likely continue to be used as an alternative to total knee replacement in younger patients and to shift weight away from an area of the knee where cartilage is being restored with a concomitant surgical procedure, according to the work group. They noted that additional research studies on the long-term efficacy of the procedure are still needed.

Topical treatments. The guideline authors gave these a strong recommendation. Gels with anti-inflammatory medication have long been available but were prescription only or of considerable cost. Now several affordable over-the-counter options with the same prescription strength can be found in pharmacies and supermarkets.

What makes these medications unique is that they have an NSAID medication in the formulation, which the vast majority of topical treatments found on shelves do not. They also benefit patients who are unable to tolerate oral NSAIDs because of gastrointestinal side effects.

Comparison with 2019 OARSI recommendations

In 2019, the Osteoarthritis Research Society International also published guidelines for the management of OA of the hand, hip, and knee.

Thomas Trojian, MD, a family medicine physician with expertise in sports medicine in York, Pa., and member of both the AAOS and OARSI recommendation committees, noted that the OARSI guidelines are meant to be practical guidelines of stepwise nonoperative treatment.

He said in an interview that “the OARSI guidelines recommend dietary weight management, education, and land-based [exercise] therapy, next topical NSAIDs, then injection therapy.”

Intra-articular steroids and viscosupplementation injection therapy in the form of hyaluronic acid derivatives continue to be a mainstay of treatment for both groups.

The AAOS group notably gave a moderate strength recommendation for intra-articular steroid injections with the caveat that the effects typically only last for 3 months. They also included newer extended-release steroid injections in the recommendation, stating that the evidence moderately suggests they provide more benefit than traditional short-acting steroid injections.
 

Methodology differs between guidelines

In the areas where the guidelines don’t fully line up, it is important to remember the methodology of each group often drives the guidelines and recommendations.

According to Yale Fillingham, MD, an orthopedic surgeon in group private practice in the greater Philadelphia area and the other cochair of the AAOS guidelines committee, the biggest difference between the AAOS and OARSI guidelines is that, although the OARSI guidelines are also grounded in the literature, the recommendation level was based on voting among panel members.

“The AAOS methodology requires the recommendation and strength of the recommendation to be dictated primarily by the best available evidence in the literature and much less on the expertise and opinion of the voting panel,” Dr. Fillingham said in an interview.

He pointed out that the AAOS voting panel can alter the guideline by adjusting the strength of the recommendation but noted it was only in very clearly defined situations. Therefore, the differences in methodology between the groups make it difficult to directly compare the two guidelines.

Multiple guidelines do, however, point to the importance of the issue. Dr. Fillingham commented: “The numerous organizations that have produced guidelines on the treatment of knee osteoarthritis are a testament to the widespread and profound impact of knee osteoarthritis on our health care system and society.”

As a member of both recommendation groups, Dr. Trojian finds both guidelines reveal the importance of understanding that knee OA is a chronic illness. “There are ways we can manage knee OA and reduce the morbidity. ... The core skills of motivational interviewing are important. Open-ended questions, affirmation, reflection, and summarizing are needed to help patients find and remove roadblocks to promote lifestyle changes.”

Dr. Brophy, Dr. Trojian, and Dr. Fillingham have disclosed no relevant financial relationships.

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

A significant literature describes efforts to reduce hospital readmissions through improving care transitions. Many approaches have been tried, alone or in combination, targeting different points across the spectrum of discharge activities. These approaches encompass interventions initiated prior to discharge, such as patient education and enhanced discharge planning; bridging interventions, such as transition coaches; and postdischarge interventions, such as home visits or early follow-up appointments. Transitions of care clinics (TOCC) attempt to improve posthospital care by providing dedicated, rapid follow-up for patients after discharge.¹

The impact of care transitions interventions is mixed, with inconsistent results across interventions and contexts. More complex, multipronged, context- and patient-sensitive interventions, however, are more likely to be associated with lower readmission rates.^2,3

In this issue of the journal, Griffin and colleagues⁴ report on their TOCC implementation. Their focus on a high-risk, rural veteran population is different from prior studies, as is their use of in-person or virtual follow-up options. While the authors describe their intervention as a TOCC, their model serves as an organizer for an interprofessional team, including hospitalists, that coordinates multiple activities that complement the postdischarge appointments: identification of high-risk patients, pharmacist-led medication reconciliation, dietary counseling, contingency planning for potential changes, follow-up on pending tests and studies, and coordination of primary care and specialty care appointments. The multipronged, patient-sensitive nature of their intervention makes their positive findings consistent with other care transition literature.

Griffin and colleagues’ reporting of their TOCC experience is worth highlighting, as they present their experience and results in a way that maximizes our ability to learn from their implementation. Unfortunately, reports of improvement initiatives often lack sufficient detail regarding the context or intervention to potentially apply their findings. Griffin and colleagues applied the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines, a standardized framework for describing improvement initiatives that captures critical contextual and intervention elements.⁵Griffin and colleagues describe their baseline readmission performance and how the TOCC model was relevant to this issue. They describe the context, including their patient population, and their intervention with sufficient detail for us to understand what they actually did. Importantly, Griffin and colleagues clearly delineate the dynamic phases of the implementation, their use of Plan-Do-Study-Act cycles to assess and improve their implementation, and the specific changes they made. The Figure clearly puts their results in the context of their program evolution, and their secondary outcomes support our understanding of program growth. Their use of a committee for ongoing monitoring could be important for ongoing adaptation and sustainability.

There are several limitations worth noting. There may have been subjectivity in teams’ decisions to refer specific patients with lower Care Assessment Need scores. We do not know why patients did not attend TOCC visits, or why they chose virtual vs in-person visits. This study was conducted within the Veterans Affairs system, where program supports, such as tablets for virtual visits and coordination among services, may be easier to implement than in other settings. Despite these limitations, we see that complex, high-risk patients benefit from a multidisciplinary, multipronged approach to care transitions. Moreover, we learned about barriers encountered during TOCC implementation and how these issues were successfully addressed. Finally, their work suggests that telehealth may be an appealing and promising component of care transition programs, but that patients may not choose this modality solely because of geography.

In this era of multisite collaborative studies and analyses of large administrative datasets, Griffin et al⁴ demonstrate that there is still much to learn from a well-done, single-site improvement study.

Funding: Drs Leykum and Penney reported funding from the Department of Veterans Affairs.

A significant literature describes efforts to reduce hospital readmissions through improving care transitions. Many approaches have been tried, alone or in combination, targeting different points across the spectrum of discharge activities. These approaches encompass interventions initiated prior to discharge, such as patient education and enhanced discharge planning; bridging interventions, such as transition coaches; and postdischarge interventions, such as home visits or early follow-up appointments. Transitions of care clinics (TOCC) attempt to improve posthospital care by providing dedicated, rapid follow-up for patients after discharge.¹

The impact of care transitions interventions is mixed, with inconsistent results across interventions and contexts. More complex, multipronged, context- and patient-sensitive interventions, however, are more likely to be associated with lower readmission rates.^2,3

In this issue of the journal, Griffin and colleagues⁴ report on their TOCC implementation. Their focus on a high-risk, rural veteran population is different from prior studies, as is their use of in-person or virtual follow-up options. While the authors describe their intervention as a TOCC, their model serves as an organizer for an interprofessional team, including hospitalists, that coordinates multiple activities that complement the postdischarge appointments: identification of high-risk patients, pharmacist-led medication reconciliation, dietary counseling, contingency planning for potential changes, follow-up on pending tests and studies, and coordination of primary care and specialty care appointments. The multipronged, patient-sensitive nature of their intervention makes their positive findings consistent with other care transition literature.

Griffin and colleagues’ reporting of their TOCC experience is worth highlighting, as they present their experience and results in a way that maximizes our ability to learn from their implementation. Unfortunately, reports of improvement initiatives often lack sufficient detail regarding the context or intervention to potentially apply their findings. Griffin and colleagues applied the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines, a standardized framework for describing improvement initiatives that captures critical contextual and intervention elements.⁵Griffin and colleagues describe their baseline readmission performance and how the TOCC model was relevant to this issue. They describe the context, including their patient population, and their intervention with sufficient detail for us to understand what they actually did. Importantly, Griffin and colleagues clearly delineate the dynamic phases of the implementation, their use of Plan-Do-Study-Act cycles to assess and improve their implementation, and the specific changes they made. The Figure clearly puts their results in the context of their program evolution, and their secondary outcomes support our understanding of program growth. Their use of a committee for ongoing monitoring could be important for ongoing adaptation and sustainability.

There are several limitations worth noting. There may have been subjectivity in teams’ decisions to refer specific patients with lower Care Assessment Need scores. We do not know why patients did not attend TOCC visits, or why they chose virtual vs in-person visits. This study was conducted within the Veterans Affairs system, where program supports, such as tablets for virtual visits and coordination among services, may be easier to implement than in other settings. Despite these limitations, we see that complex, high-risk patients benefit from a multidisciplinary, multipronged approach to care transitions. Moreover, we learned about barriers encountered during TOCC implementation and how these issues were successfully addressed. Finally, their work suggests that telehealth may be an appealing and promising component of care transition programs, but that patients may not choose this modality solely because of geography.

In this era of multisite collaborative studies and analyses of large administrative datasets, Griffin et al⁴ demonstrate that there is still much to learn from a well-done, single-site improvement study.

Funding: Drs Leykum and Penney reported funding from the Department of Veterans Affairs.

A significant literature describes efforts to reduce hospital readmissions through improving care transitions. Many approaches have been tried, alone or in combination, targeting different points across the spectrum of discharge activities. These approaches encompass interventions initiated prior to discharge, such as patient education and enhanced discharge planning; bridging interventions, such as transition coaches; and postdischarge interventions, such as home visits or early follow-up appointments. Transitions of care clinics (TOCC) attempt to improve posthospital care by providing dedicated, rapid follow-up for patients after discharge.¹

The impact of care transitions interventions is mixed, with inconsistent results across interventions and contexts. More complex, multipronged, context- and patient-sensitive interventions, however, are more likely to be associated with lower readmission rates.^2,3

In this issue of the journal, Griffin and colleagues⁴ report on their TOCC implementation. Their focus on a high-risk, rural veteran population is different from prior studies, as is their use of in-person or virtual follow-up options. While the authors describe their intervention as a TOCC, their model serves as an organizer for an interprofessional team, including hospitalists, that coordinates multiple activities that complement the postdischarge appointments: identification of high-risk patients, pharmacist-led medication reconciliation, dietary counseling, contingency planning for potential changes, follow-up on pending tests and studies, and coordination of primary care and specialty care appointments. The multipronged, patient-sensitive nature of their intervention makes their positive findings consistent with other care transition literature.

Griffin and colleagues’ reporting of their TOCC experience is worth highlighting, as they present their experience and results in a way that maximizes our ability to learn from their implementation. Unfortunately, reports of improvement initiatives often lack sufficient detail regarding the context or intervention to potentially apply their findings. Griffin and colleagues applied the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines, a standardized framework for describing improvement initiatives that captures critical contextual and intervention elements.⁵Griffin and colleagues describe their baseline readmission performance and how the TOCC model was relevant to this issue. They describe the context, including their patient population, and their intervention with sufficient detail for us to understand what they actually did. Importantly, Griffin and colleagues clearly delineate the dynamic phases of the implementation, their use of Plan-Do-Study-Act cycles to assess and improve their implementation, and the specific changes they made. The Figure clearly puts their results in the context of their program evolution, and their secondary outcomes support our understanding of program growth. Their use of a committee for ongoing monitoring could be important for ongoing adaptation and sustainability.

There are several limitations worth noting. There may have been subjectivity in teams’ decisions to refer specific patients with lower Care Assessment Need scores. We do not know why patients did not attend TOCC visits, or why they chose virtual vs in-person visits. This study was conducted within the Veterans Affairs system, where program supports, such as tablets for virtual visits and coordination among services, may be easier to implement than in other settings. Despite these limitations, we see that complex, high-risk patients benefit from a multidisciplinary, multipronged approach to care transitions. Moreover, we learned about barriers encountered during TOCC implementation and how these issues were successfully addressed. Finally, their work suggests that telehealth may be an appealing and promising component of care transition programs, but that patients may not choose this modality solely because of geography.

In this era of multisite collaborative studies and analyses of large administrative datasets, Griffin et al⁴ demonstrate that there is still much to learn from a well-done, single-site improvement study.

Funding: Drs Leykum and Penney reported funding from the Department of Veterans Affairs.

The U.S. Food and Drug Administration is informing health care providers of potential differences in procedural outcomes between men and women undergoing transcatheter left atrial appendage occlusion (LAAO).

The agency said it is evaluating a real-world study, published in JAMA Cardiology, of 49,357 patients in the National Cardiovascular Data Registry LAAO Registry that suggested women might be at greater risk than men for procedural outcomes, including major adverse events after device implant.

“The FDA recognizes the limitations of these data, including that the study was not randomized, only included one LAAO device (the first-generation Watchman device), and did not include longer-term outcomes beyond in-hospital events. However, the analysis provides results from a large registry of patients treated with LAAO implants in the U.S.,” the agency said in its letter to health care providers Sept. 27.

As reported last month, the study by Darden et al showed a significantly higher rate of adverse procedural events in women than in men, including any adverse events (6.3% vs. 3.9%; P < .001), any major adverse events (4.1% vs. 2.0%; P < .001), and hospital stay longer than 1 day (16.0% vs. 11.6%; P < .001). Procedure-associated death was 0.3% in women and 0.1% in men.

The agency noted that the number of patients in the LAAO Registry analysis was much larger than the number of patients in the premarket studies of the Watchman device that supported its approval and in the premarket studies for the other approved LAAO devices.

LAAO devices are indicated to reduce the risk for thromboembolism from the left atrial appendage in patients with nonvalvular atrial fibrillation who are not good candidates for long-term anticoagulation. LAAO devices currently marketed in the United States are Boston Scientific’s Watchman and Watchman FLX devices and Abbott Medical’s Amplatzer Amulet device.

“Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use,” the letter states.

The FDA will work with device manufacturers to evaluate the potential issue, including a review of available premarket and postapproval study data and other available real-world, postmarket datasets, the letter notes.

The agency will also work with device manufacturers, investigators, and the LAAO Registry to try to identify the causes of procedural outcome differences between women and men.

In the letter, the FDA recommends health care providers continue monitoring patients who have been treated with LAAO devices in accordance with the current standard of care. They should also discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation as part of shared clinical decision-making.

Any adverse events or suspected adverse events experienced by patients with LAAO devices should also be reported to the FDA through MedWatch, its adverse event reporting program.

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

The U.S. Food and Drug Administration is informing health care providers of potential differences in procedural outcomes between men and women undergoing transcatheter left atrial appendage occlusion (LAAO).

The agency said it is evaluating a real-world study, published in JAMA Cardiology, of 49,357 patients in the National Cardiovascular Data Registry LAAO Registry that suggested women might be at greater risk than men for procedural outcomes, including major adverse events after device implant.

“The FDA recognizes the limitations of these data, including that the study was not randomized, only included one LAAO device (the first-generation Watchman device), and did not include longer-term outcomes beyond in-hospital events. However, the analysis provides results from a large registry of patients treated with LAAO implants in the U.S.,” the agency said in its letter to health care providers Sept. 27.

As reported last month, the study by Darden et al showed a significantly higher rate of adverse procedural events in women than in men, including any adverse events (6.3% vs. 3.9%; P < .001), any major adverse events (4.1% vs. 2.0%; P < .001), and hospital stay longer than 1 day (16.0% vs. 11.6%; P < .001). Procedure-associated death was 0.3% in women and 0.1% in men.

The agency noted that the number of patients in the LAAO Registry analysis was much larger than the number of patients in the premarket studies of the Watchman device that supported its approval and in the premarket studies for the other approved LAAO devices.

LAAO devices are indicated to reduce the risk for thromboembolism from the left atrial appendage in patients with nonvalvular atrial fibrillation who are not good candidates for long-term anticoagulation. LAAO devices currently marketed in the United States are Boston Scientific’s Watchman and Watchman FLX devices and Abbott Medical’s Amplatzer Amulet device.

“Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use,” the letter states.

The FDA will work with device manufacturers to evaluate the potential issue, including a review of available premarket and postapproval study data and other available real-world, postmarket datasets, the letter notes.

The agency will also work with device manufacturers, investigators, and the LAAO Registry to try to identify the causes of procedural outcome differences between women and men.

In the letter, the FDA recommends health care providers continue monitoring patients who have been treated with LAAO devices in accordance with the current standard of care. They should also discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation as part of shared clinical decision-making.

Any adverse events or suspected adverse events experienced by patients with LAAO devices should also be reported to the FDA through MedWatch, its adverse event reporting program.

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

The U.S. Food and Drug Administration is informing health care providers of potential differences in procedural outcomes between men and women undergoing transcatheter left atrial appendage occlusion (LAAO).

The agency said it is evaluating a real-world study, published in JAMA Cardiology, of 49,357 patients in the National Cardiovascular Data Registry LAAO Registry that suggested women might be at greater risk than men for procedural outcomes, including major adverse events after device implant.

“The FDA recognizes the limitations of these data, including that the study was not randomized, only included one LAAO device (the first-generation Watchman device), and did not include longer-term outcomes beyond in-hospital events. However, the analysis provides results from a large registry of patients treated with LAAO implants in the U.S.,” the agency said in its letter to health care providers Sept. 27.

As reported last month, the study by Darden et al showed a significantly higher rate of adverse procedural events in women than in men, including any adverse events (6.3% vs. 3.9%; P < .001), any major adverse events (4.1% vs. 2.0%; P < .001), and hospital stay longer than 1 day (16.0% vs. 11.6%; P < .001). Procedure-associated death was 0.3% in women and 0.1% in men.

The agency noted that the number of patients in the LAAO Registry analysis was much larger than the number of patients in the premarket studies of the Watchman device that supported its approval and in the premarket studies for the other approved LAAO devices.

LAAO devices are indicated to reduce the risk for thromboembolism from the left atrial appendage in patients with nonvalvular atrial fibrillation who are not good candidates for long-term anticoagulation. LAAO devices currently marketed in the United States are Boston Scientific’s Watchman and Watchman FLX devices and Abbott Medical’s Amplatzer Amulet device.

“Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use,” the letter states.

The FDA will work with device manufacturers to evaluate the potential issue, including a review of available premarket and postapproval study data and other available real-world, postmarket datasets, the letter notes.

The agency will also work with device manufacturers, investigators, and the LAAO Registry to try to identify the causes of procedural outcome differences between women and men.

In the letter, the FDA recommends health care providers continue monitoring patients who have been treated with LAAO devices in accordance with the current standard of care. They should also discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation as part of shared clinical decision-making.

Any adverse events or suspected adverse events experienced by patients with LAAO devices should also be reported to the FDA through MedWatch, its adverse event reporting program.

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

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.