MDedge Neurology

Growing up, my dad would often go to his law office on weekends to get work done.

As a kid I didn’t really understand this. Dad had an office at home, and could close the door if he needed to. Usually he did this, but sometimes he left to go to his REAL office.

And now ... I sometimes do the same thing.

I don’t see patients on Fridays these days. In the postpandemic world my schedule still hasn’t returned to normal (maybe it never will and this is the new normal), and with research and case reviews and other stuff it seemed logical to just work from home and do them that day. My staff works from home, so if I’m not seeing patients, why can’t I?

After a few Fridays of this, I began going to my empty office, too, and understood where my dad was coming from.

My little solo office, as non-fancy as it is (the carpeting and interior are all from 1993), is quiet. From my back office I can’t hear the corridor hustle and bustle of people going to their appointments or arguing on a cell phone. Just the hum of the air conditioner and the occasional few seconds of a car alarm outside. If I put on iTunes no one complains about my musical tastes.

There isn’t much to do there BUT work, which is the idea. The building’s wifi is too slow to stream or watch Youtube. I’m not tempted to work on a puzzle with my daughter, take a book off a shelf, play with my dogs, or go down the hall for a nap. All the little things we do to procrastinate aren’t there, like convincing myself that I need to clean the pool or balance the checkbook ASAP.

I don’t have the distractions of my dogs barking at passing cars, or kids going up and down the hall, or the phone ringing with people asking who I’m voting for.

My little office is a private oasis, of sorts. Quiet and undisturbed.

Not quite Superman’s Fortress of Solitude, but close enough for me.

And, with all due respect to the Man of Steel, the Fortress of Solitude doesn’t have a Keurig.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Growing up, my dad would often go to his law office on weekends to get work done.

As a kid I didn’t really understand this. Dad had an office at home, and could close the door if he needed to. Usually he did this, but sometimes he left to go to his REAL office.

And now ... I sometimes do the same thing.

I don’t see patients on Fridays these days. In the postpandemic world my schedule still hasn’t returned to normal (maybe it never will and this is the new normal), and with research and case reviews and other stuff it seemed logical to just work from home and do them that day. My staff works from home, so if I’m not seeing patients, why can’t I?

After a few Fridays of this, I began going to my empty office, too, and understood where my dad was coming from.

My little solo office, as non-fancy as it is (the carpeting and interior are all from 1993), is quiet. From my back office I can’t hear the corridor hustle and bustle of people going to their appointments or arguing on a cell phone. Just the hum of the air conditioner and the occasional few seconds of a car alarm outside. If I put on iTunes no one complains about my musical tastes.

There isn’t much to do there BUT work, which is the idea. The building’s wifi is too slow to stream or watch Youtube. I’m not tempted to work on a puzzle with my daughter, take a book off a shelf, play with my dogs, or go down the hall for a nap. All the little things we do to procrastinate aren’t there, like convincing myself that I need to clean the pool or balance the checkbook ASAP.

I don’t have the distractions of my dogs barking at passing cars, or kids going up and down the hall, or the phone ringing with people asking who I’m voting for.

My little office is a private oasis, of sorts. Quiet and undisturbed.

Not quite Superman’s Fortress of Solitude, but close enough for me.

And, with all due respect to the Man of Steel, the Fortress of Solitude doesn’t have a Keurig.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Growing up, my dad would often go to his law office on weekends to get work done.

As a kid I didn’t really understand this. Dad had an office at home, and could close the door if he needed to. Usually he did this, but sometimes he left to go to his REAL office.

And now ... I sometimes do the same thing.

I don’t see patients on Fridays these days. In the postpandemic world my schedule still hasn’t returned to normal (maybe it never will and this is the new normal), and with research and case reviews and other stuff it seemed logical to just work from home and do them that day. My staff works from home, so if I’m not seeing patients, why can’t I?

After a few Fridays of this, I began going to my empty office, too, and understood where my dad was coming from.

My little solo office, as non-fancy as it is (the carpeting and interior are all from 1993), is quiet. From my back office I can’t hear the corridor hustle and bustle of people going to their appointments or arguing on a cell phone. Just the hum of the air conditioner and the occasional few seconds of a car alarm outside. If I put on iTunes no one complains about my musical tastes.

There isn’t much to do there BUT work, which is the idea. The building’s wifi is too slow to stream or watch Youtube. I’m not tempted to work on a puzzle with my daughter, take a book off a shelf, play with my dogs, or go down the hall for a nap. All the little things we do to procrastinate aren’t there, like convincing myself that I need to clean the pool or balance the checkbook ASAP.

I don’t have the distractions of my dogs barking at passing cars, or kids going up and down the hall, or the phone ringing with people asking who I’m voting for.

My little office is a private oasis, of sorts. Quiet and undisturbed.

Not quite Superman’s Fortress of Solitude, but close enough for me.

And, with all due respect to the Man of Steel, the Fortress of Solitude doesn’t have a Keurig.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A U.S. Food and Drug Administration advisory panel has rejected the atypical antipsychotic pimavanserin (Nuplazid, Acadia Pharmaceuticals) for the treatment of Alzheimer’s disease psychosis (ADP).

In a 9-3 vote, the Psychopharmacologic Drugs Advisory Committee (PDAC) found that the drug’s manufacturer failed to offer convincing evidence of its efficacy in patients with ADP.

The June 17 rejection was the second rejection in as many years for a new indication for pimavanserin, which was approved in 2016 for Parkinson’s disease psychosis (PDP).

In April 2021, the FDA denied Acadia’s supplemental new drug application to expand the drug’s indication to include the treatment of all dementia-related psychosis, regardless of the underlying cause of dementia, citing issues with two studies the company presented as evidence of efficacy.

Waldemarus/iStock/Getty Images Plus

Lack of efficacy

Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders.

When it rejected Acadia’s original, broader application for pimavanserin for all dementia-related psychosis, the FDA found that the HARMONY phase 3 trial, previously covered by this news organization, was underpowered to assess efficacy in specific dementia patient subgroups and lacked statistical significance of efficacy in patients with AD. In addition, it noted that overall findings appeared to be driven by results in patients with Parkinson’s disease dementia, a condition already covered by the approved indication.

The FDA found that the second study, referred to in the June 17 hearing as Study 019, which was also previously reported by this news organization, was not “an adequate and well-controlled study.”

Specifically, the agency raised concerns about “protocol deviations,” such as the inclusion of patients who lacked clear documentation that psychotic symptoms developed after an AD diagnosis had been established and patients who received exclusionary medications at the time of randomization.

Discussions between Acadia and the FDA continued over the past year, with the company submitting new analyses and responses. An FDA briefing document published in advance of the committee meeting seemed to suggest the agency was satisfied with Acadia’s response.
 

Lack of diversity

The advisory committee disagreed, pointing to the same concerns raised last year. Members raised concerns about patient diversity in the HARMONY trial, which included an almost entirely White and mostly male study population.

In addition, although the findings at 26 weeks did demonstrate a marked improvement in psychosis symptoms overall, committee members noted that, again, those findings were largely driven by efficacy in patients with Parkinson’s disease dementia, for which the drug is already approved.

When discussing the phase 2 Study 019, the committee noted that while the study met the primary outcome of improvement in psychosis at 6 weeks, those positive responses were not found at any other timepoint in the 12-week study.  

“While it might have had a positive numerical effect in the study, the evidence is really not there to support it,” Dr. Follmann said.

Dr. Follmann and other committee members called for additional trials that focus on patients with Alzheimer’s disease, have a longer follow-up, and include more gender and racial diversity in the study population. They also called for more information about any off-label use of pimavanserin for ADP since it was approved for PDP in 2016.
 

An unmet need

Most individuals who testified during the public comment period pleaded with the committee to vote in favor of the new indication, sharing stories of family members and patients with ADP.

“I have been caring for and studying patients with Alzheimer’s disease and other dementias for more than 30 years, and I can tell you very simply that if left untreated, psychosis has significant and sometimes devastating consequences for our patients,” said Pierre Tariot, MD, director of the Banner Alzheimer’s Institute and a research professor of psychiatry at the University of Arizona College of Medicine, Tucson, and an investigator on the HARMONY trial.

Those on the committee who voted against the application were quick to agree that lack of an approved treatment for ADP presents a hardship.

“I’m a neurologist who has cared for patients for more than 20 years,” said Madhav R. Thambisetty, MD, PhD, senior investigator for the National Institute on Aging and an adjunct professor of neurology at Johns Hopkins University School of Medicine, Baltimore. “I recognize the unmet need in the field, I just think that the unmet need should not be a justification to cut corners.”

The committee did not focus on drug safety or unmet need in its deliberations, although information on both were presented during the meeting.

Commenting on his “no” vote, PDAC member Walter S. Dunn, MD, PhD, assistant clinical professor of psychiatry at the University of California, Los Angeles, and director of Interventional Psychiatry Service at West Los Angeles Veterans Affairs Medical Center, said he hopes that the FDA will consider those issues more broadly as they complete their review.

“The questions before the committee have been narrow and precise, so I trust the agency will take a broader approach in their final decision about approval,” Dr. Dunn said.

Commenting on the decision, Howard Fillit, MD, cofounder and chief science officer, Alzheimer’s Drug Discovery Foundation, called the news disappointing, “but while the unmet need for a treatment for ADP is clear, it is vital that approved treatments meet stringent safety and efficacy criteria so we can offer patients medications with clear benefits.”

The FDA will make its final decision by August 4.

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

A U.S. Food and Drug Administration advisory panel has rejected the atypical antipsychotic pimavanserin (Nuplazid, Acadia Pharmaceuticals) for the treatment of Alzheimer’s disease psychosis (ADP).

In a 9-3 vote, the Psychopharmacologic Drugs Advisory Committee (PDAC) found that the drug’s manufacturer failed to offer convincing evidence of its efficacy in patients with ADP.

The June 17 rejection was the second rejection in as many years for a new indication for pimavanserin, which was approved in 2016 for Parkinson’s disease psychosis (PDP).

In April 2021, the FDA denied Acadia’s supplemental new drug application to expand the drug’s indication to include the treatment of all dementia-related psychosis, regardless of the underlying cause of dementia, citing issues with two studies the company presented as evidence of efficacy.

Waldemarus/iStock/Getty Images Plus

Lack of efficacy

Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders.

When it rejected Acadia’s original, broader application for pimavanserin for all dementia-related psychosis, the FDA found that the HARMONY phase 3 trial, previously covered by this news organization, was underpowered to assess efficacy in specific dementia patient subgroups and lacked statistical significance of efficacy in patients with AD. In addition, it noted that overall findings appeared to be driven by results in patients with Parkinson’s disease dementia, a condition already covered by the approved indication.

The FDA found that the second study, referred to in the June 17 hearing as Study 019, which was also previously reported by this news organization, was not “an adequate and well-controlled study.”

Specifically, the agency raised concerns about “protocol deviations,” such as the inclusion of patients who lacked clear documentation that psychotic symptoms developed after an AD diagnosis had been established and patients who received exclusionary medications at the time of randomization.

Discussions between Acadia and the FDA continued over the past year, with the company submitting new analyses and responses. An FDA briefing document published in advance of the committee meeting seemed to suggest the agency was satisfied with Acadia’s response.
 

Lack of diversity

The advisory committee disagreed, pointing to the same concerns raised last year. Members raised concerns about patient diversity in the HARMONY trial, which included an almost entirely White and mostly male study population.

In addition, although the findings at 26 weeks did demonstrate a marked improvement in psychosis symptoms overall, committee members noted that, again, those findings were largely driven by efficacy in patients with Parkinson’s disease dementia, for which the drug is already approved.

When discussing the phase 2 Study 019, the committee noted that while the study met the primary outcome of improvement in psychosis at 6 weeks, those positive responses were not found at any other timepoint in the 12-week study.  

“While it might have had a positive numerical effect in the study, the evidence is really not there to support it,” Dr. Follmann said.

Dr. Follmann and other committee members called for additional trials that focus on patients with Alzheimer’s disease, have a longer follow-up, and include more gender and racial diversity in the study population. They also called for more information about any off-label use of pimavanserin for ADP since it was approved for PDP in 2016.
 

An unmet need

Most individuals who testified during the public comment period pleaded with the committee to vote in favor of the new indication, sharing stories of family members and patients with ADP.

“I have been caring for and studying patients with Alzheimer’s disease and other dementias for more than 30 years, and I can tell you very simply that if left untreated, psychosis has significant and sometimes devastating consequences for our patients,” said Pierre Tariot, MD, director of the Banner Alzheimer’s Institute and a research professor of psychiatry at the University of Arizona College of Medicine, Tucson, and an investigator on the HARMONY trial.

Those on the committee who voted against the application were quick to agree that lack of an approved treatment for ADP presents a hardship.

“I’m a neurologist who has cared for patients for more than 20 years,” said Madhav R. Thambisetty, MD, PhD, senior investigator for the National Institute on Aging and an adjunct professor of neurology at Johns Hopkins University School of Medicine, Baltimore. “I recognize the unmet need in the field, I just think that the unmet need should not be a justification to cut corners.”

The committee did not focus on drug safety or unmet need in its deliberations, although information on both were presented during the meeting.

Commenting on his “no” vote, PDAC member Walter S. Dunn, MD, PhD, assistant clinical professor of psychiatry at the University of California, Los Angeles, and director of Interventional Psychiatry Service at West Los Angeles Veterans Affairs Medical Center, said he hopes that the FDA will consider those issues more broadly as they complete their review.

“The questions before the committee have been narrow and precise, so I trust the agency will take a broader approach in their final decision about approval,” Dr. Dunn said.

Commenting on the decision, Howard Fillit, MD, cofounder and chief science officer, Alzheimer’s Drug Discovery Foundation, called the news disappointing, “but while the unmet need for a treatment for ADP is clear, it is vital that approved treatments meet stringent safety and efficacy criteria so we can offer patients medications with clear benefits.”

The FDA will make its final decision by August 4.

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

A U.S. Food and Drug Administration advisory panel has rejected the atypical antipsychotic pimavanserin (Nuplazid, Acadia Pharmaceuticals) for the treatment of Alzheimer’s disease psychosis (ADP).

In a 9-3 vote, the Psychopharmacologic Drugs Advisory Committee (PDAC) found that the drug’s manufacturer failed to offer convincing evidence of its efficacy in patients with ADP.

The June 17 rejection was the second rejection in as many years for a new indication for pimavanserin, which was approved in 2016 for Parkinson’s disease psychosis (PDP).

In April 2021, the FDA denied Acadia’s supplemental new drug application to expand the drug’s indication to include the treatment of all dementia-related psychosis, regardless of the underlying cause of dementia, citing issues with two studies the company presented as evidence of efficacy.

Waldemarus/iStock/Getty Images Plus

Lack of efficacy

Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders.

When it rejected Acadia’s original, broader application for pimavanserin for all dementia-related psychosis, the FDA found that the HARMONY phase 3 trial, previously covered by this news organization, was underpowered to assess efficacy in specific dementia patient subgroups and lacked statistical significance of efficacy in patients with AD. In addition, it noted that overall findings appeared to be driven by results in patients with Parkinson’s disease dementia, a condition already covered by the approved indication.

The FDA found that the second study, referred to in the June 17 hearing as Study 019, which was also previously reported by this news organization, was not “an adequate and well-controlled study.”

Specifically, the agency raised concerns about “protocol deviations,” such as the inclusion of patients who lacked clear documentation that psychotic symptoms developed after an AD diagnosis had been established and patients who received exclusionary medications at the time of randomization.

Discussions between Acadia and the FDA continued over the past year, with the company submitting new analyses and responses. An FDA briefing document published in advance of the committee meeting seemed to suggest the agency was satisfied with Acadia’s response.
 

Lack of diversity

The advisory committee disagreed, pointing to the same concerns raised last year. Members raised concerns about patient diversity in the HARMONY trial, which included an almost entirely White and mostly male study population.

In addition, although the findings at 26 weeks did demonstrate a marked improvement in psychosis symptoms overall, committee members noted that, again, those findings were largely driven by efficacy in patients with Parkinson’s disease dementia, for which the drug is already approved.

When discussing the phase 2 Study 019, the committee noted that while the study met the primary outcome of improvement in psychosis at 6 weeks, those positive responses were not found at any other timepoint in the 12-week study.  

“While it might have had a positive numerical effect in the study, the evidence is really not there to support it,” Dr. Follmann said.

Dr. Follmann and other committee members called for additional trials that focus on patients with Alzheimer’s disease, have a longer follow-up, and include more gender and racial diversity in the study population. They also called for more information about any off-label use of pimavanserin for ADP since it was approved for PDP in 2016.
 

An unmet need

Most individuals who testified during the public comment period pleaded with the committee to vote in favor of the new indication, sharing stories of family members and patients with ADP.

“I have been caring for and studying patients with Alzheimer’s disease and other dementias for more than 30 years, and I can tell you very simply that if left untreated, psychosis has significant and sometimes devastating consequences for our patients,” said Pierre Tariot, MD, director of the Banner Alzheimer’s Institute and a research professor of psychiatry at the University of Arizona College of Medicine, Tucson, and an investigator on the HARMONY trial.

Those on the committee who voted against the application were quick to agree that lack of an approved treatment for ADP presents a hardship.

“I’m a neurologist who has cared for patients for more than 20 years,” said Madhav R. Thambisetty, MD, PhD, senior investigator for the National Institute on Aging and an adjunct professor of neurology at Johns Hopkins University School of Medicine, Baltimore. “I recognize the unmet need in the field, I just think that the unmet need should not be a justification to cut corners.”

The committee did not focus on drug safety or unmet need in its deliberations, although information on both were presented during the meeting.

Commenting on his “no” vote, PDAC member Walter S. Dunn, MD, PhD, assistant clinical professor of psychiatry at the University of California, Los Angeles, and director of Interventional Psychiatry Service at West Los Angeles Veterans Affairs Medical Center, said he hopes that the FDA will consider those issues more broadly as they complete their review.

“The questions before the committee have been narrow and precise, so I trust the agency will take a broader approach in their final decision about approval,” Dr. Dunn said.

Commenting on the decision, Howard Fillit, MD, cofounder and chief science officer, Alzheimer’s Drug Discovery Foundation, called the news disappointing, “but while the unmet need for a treatment for ADP is clear, it is vital that approved treatments meet stringent safety and efficacy criteria so we can offer patients medications with clear benefits.”

The FDA will make its final decision by August 4.

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

The following highlights are a brief overview of guideline updates, drug approvals, and diagnostics relevant to geriatric medicine from June 2021 to April 2022, some of which were discussed at the American Geriatrics Society conference in May. I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).

Aspirin for primary prevention

It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.¹

The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.

While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.²

Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
 

Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia

One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.

Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.⁴

Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.

Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.⁵

Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.

In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.⁶
 

Overdiagnosis of CKD in older adults

The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m² for adults aged 65 and older.⁷

The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.⁸ In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.

A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.

These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
 

Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.

References

1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.

2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.

3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.

4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.

5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.

6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.

7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.

8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.

The following highlights are a brief overview of guideline updates, drug approvals, and diagnostics relevant to geriatric medicine from June 2021 to April 2022, some of which were discussed at the American Geriatrics Society conference in May. I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).

Aspirin for primary prevention

It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.¹

The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.

While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.²

Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
 

Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia

One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.

Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.⁴

Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.

Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.⁵

Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.

In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.⁶
 

Overdiagnosis of CKD in older adults

The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m² for adults aged 65 and older.⁷

The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.⁸ In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.

A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.

These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
 

Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.

References

1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.

2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.

3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.

4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.

5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.

6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.

7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.

8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.

The following highlights are a brief overview of guideline updates, drug approvals, and diagnostics relevant to geriatric medicine from June 2021 to April 2022, some of which were discussed at the American Geriatrics Society conference in May. I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).

Aspirin for primary prevention

It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.¹

The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.

While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.²

Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
 

Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia

One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.

Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.⁴

Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.

Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.⁵

Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.

In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.⁶
 

Overdiagnosis of CKD in older adults

The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m² for adults aged 65 and older.⁷

The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.⁸ In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.

A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.

These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
 

Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.

References

1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.

2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.

3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.

4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.

5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.

6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.

7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.

8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.

Symptoms of obstructive sleep apnea (OSA) were significantly more common in children with autism spectrum disorder (ASD), compared with controls, based on data from 166 individuals up to age 18 years.

Autism spectrum disorder affects approximately 1 in 54 children in the United States, and recent studies have shown an increased risk of obstructive sleep apnea in this population, compared with the general pediatric population, wrote Pooja Santapuram, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.

In a study published in the International Journal of Pediatric Ototrhinolaryngology , the researchers reviewed data from 166 children and adolescents up to 18 years of age with OSA who underwent adenotonsillectomy at a single center between 2019 and 2021. The primary objective was to assess OSA symptoms in children with and without ASD. The study population included 75 children with ASD and 91 controls. The average age of both the ASD group and control group was approximately 73 months.
 

OSA meets ASD

Obstructive sleep apnea is common in autism spectrum disorder. Children with OSA can present with a range of symptoms, including loud snoring, excessive daytime sleepiness, and changes in cognitive function. Some of these symptoms can overlap with and exacerbate symptoms of ASD, potentially delaying OSA diagnosis in children with both conditions. The primary objective of this study was to assess between-group difference in OSA symptomatology and age at OSA diagnosis in children with and without ASD. To do so, a retrospective chart review was conducted on the 166 pediatric patients.

Overall, significantly more OSA symptoms were reported in children with ASD, compared with controls (P < .001).

Lower autism severity was associated with an increased number of reported OSA symptoms (P = .006). There was not a significant between-group difference in age at OSA diagnosis (P = .999); however, lower autism severity was also associated with an increased age at diagnosis (P = .002). These findings suggest that OSA may present with a higher symptom burden in children with ASD, and children with lower ASD severity often experience delays in OSA diagnosis.

Interestingly, despite the known associations between obesity and OSA, children with an increased body mass index were not diagnosed with OSA at an earlier age in this sample population, the researchers indicated.

Because the current study revealed that children with less severe ASD are more likely to report an increased number of OSA symptoms and be diagnosed at a later age than children without ASD, clinicians should have a heightened sense for OSA evaluation in children with ASD, particularly in children with a lower severity of ASD and an increased BMI, the researchers concluded.

The research study was not externally funded, and the researchers reported that they had no conflicts of interest.

Symptoms of obstructive sleep apnea (OSA) were significantly more common in children with autism spectrum disorder (ASD), compared with controls, based on data from 166 individuals up to age 18 years.

Autism spectrum disorder affects approximately 1 in 54 children in the United States, and recent studies have shown an increased risk of obstructive sleep apnea in this population, compared with the general pediatric population, wrote Pooja Santapuram, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.

In a study published in the International Journal of Pediatric Ototrhinolaryngology , the researchers reviewed data from 166 children and adolescents up to 18 years of age with OSA who underwent adenotonsillectomy at a single center between 2019 and 2021. The primary objective was to assess OSA symptoms in children with and without ASD. The study population included 75 children with ASD and 91 controls. The average age of both the ASD group and control group was approximately 73 months.
 

OSA meets ASD

Obstructive sleep apnea is common in autism spectrum disorder. Children with OSA can present with a range of symptoms, including loud snoring, excessive daytime sleepiness, and changes in cognitive function. Some of these symptoms can overlap with and exacerbate symptoms of ASD, potentially delaying OSA diagnosis in children with both conditions. The primary objective of this study was to assess between-group difference in OSA symptomatology and age at OSA diagnosis in children with and without ASD. To do so, a retrospective chart review was conducted on the 166 pediatric patients.

Overall, significantly more OSA symptoms were reported in children with ASD, compared with controls (P < .001).

Lower autism severity was associated with an increased number of reported OSA symptoms (P = .006). There was not a significant between-group difference in age at OSA diagnosis (P = .999); however, lower autism severity was also associated with an increased age at diagnosis (P = .002). These findings suggest that OSA may present with a higher symptom burden in children with ASD, and children with lower ASD severity often experience delays in OSA diagnosis.

Interestingly, despite the known associations between obesity and OSA, children with an increased body mass index were not diagnosed with OSA at an earlier age in this sample population, the researchers indicated.

Because the current study revealed that children with less severe ASD are more likely to report an increased number of OSA symptoms and be diagnosed at a later age than children without ASD, clinicians should have a heightened sense for OSA evaluation in children with ASD, particularly in children with a lower severity of ASD and an increased BMI, the researchers concluded.

The research study was not externally funded, and the researchers reported that they had no conflicts of interest.

Symptoms of obstructive sleep apnea (OSA) were significantly more common in children with autism spectrum disorder (ASD), compared with controls, based on data from 166 individuals up to age 18 years.

Autism spectrum disorder affects approximately 1 in 54 children in the United States, and recent studies have shown an increased risk of obstructive sleep apnea in this population, compared with the general pediatric population, wrote Pooja Santapuram, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.

In a study published in the International Journal of Pediatric Ototrhinolaryngology , the researchers reviewed data from 166 children and adolescents up to 18 years of age with OSA who underwent adenotonsillectomy at a single center between 2019 and 2021. The primary objective was to assess OSA symptoms in children with and without ASD. The study population included 75 children with ASD and 91 controls. The average age of both the ASD group and control group was approximately 73 months.
 

OSA meets ASD

Obstructive sleep apnea is common in autism spectrum disorder. Children with OSA can present with a range of symptoms, including loud snoring, excessive daytime sleepiness, and changes in cognitive function. Some of these symptoms can overlap with and exacerbate symptoms of ASD, potentially delaying OSA diagnosis in children with both conditions. The primary objective of this study was to assess between-group difference in OSA symptomatology and age at OSA diagnosis in children with and without ASD. To do so, a retrospective chart review was conducted on the 166 pediatric patients.

Overall, significantly more OSA symptoms were reported in children with ASD, compared with controls (P < .001).

Lower autism severity was associated with an increased number of reported OSA symptoms (P = .006). There was not a significant between-group difference in age at OSA diagnosis (P = .999); however, lower autism severity was also associated with an increased age at diagnosis (P = .002). These findings suggest that OSA may present with a higher symptom burden in children with ASD, and children with lower ASD severity often experience delays in OSA diagnosis.

Interestingly, despite the known associations between obesity and OSA, children with an increased body mass index were not diagnosed with OSA at an earlier age in this sample population, the researchers indicated.

Because the current study revealed that children with less severe ASD are more likely to report an increased number of OSA symptoms and be diagnosed at a later age than children without ASD, clinicians should have a heightened sense for OSA evaluation in children with ASD, particularly in children with a lower severity of ASD and an increased BMI, the researchers concluded.

The research study was not externally funded, and the researchers reported that they had no conflicts of interest.

“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6

Lament is making a comeback. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”

“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.

Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.

On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.

Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6

Lament is making a comeback. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”

“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.

Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.

On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.

Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6

Lament is making a comeback. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”

“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.

Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.

On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.

Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

In a surprising discovery that flies in the face of conventional medicine, McGill University researchers report that treating pain with anti-inflammatory medication, like ibuprofen or aspirin, may promote pain in the long term.

The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.

“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
 

Inflammation: Nature’s pain reliever

Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.

“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”

To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.

The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.

“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
 

Rethinking how we treat pain

Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.

Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.

“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”

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

In a surprising discovery that flies in the face of conventional medicine, McGill University researchers report that treating pain with anti-inflammatory medication, like ibuprofen or aspirin, may promote pain in the long term.

The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.

“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
 

Inflammation: Nature’s pain reliever

Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.

“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”

To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.

The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.

“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
 

Rethinking how we treat pain

Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.

Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.

“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”

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

In a surprising discovery that flies in the face of conventional medicine, McGill University researchers report that treating pain with anti-inflammatory medication, like ibuprofen or aspirin, may promote pain in the long term.

The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.

“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
 

Inflammation: Nature’s pain reliever

Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.

“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”

To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.

The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.

“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
 

Rethinking how we treat pain

Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.

Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.

“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”

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

DENVER – More than a weight-loss operation, bariatric surgery can also relieve migraine, possibly because of links between head pain and the gut, a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.

As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”

The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.

“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”

Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.

Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.

Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”

Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”

She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”

Dr. McVige reported multiple disclosures related to research funding and speaker fees.

DENVER – More than a weight-loss operation, bariatric surgery can also relieve migraine, possibly because of links between head pain and the gut, a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.

As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”

The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.

“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”

Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.

Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.

Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”

Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”

She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”

Dr. McVige reported multiple disclosures related to research funding and speaker fees.

DENVER – More than a weight-loss operation, bariatric surgery can also relieve migraine, possibly because of links between head pain and the gut, a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.

As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”

The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.

“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”

Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.

Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.

Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”

Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”

She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”

Dr. McVige reported multiple disclosures related to research funding and speaker fees.

DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.

However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”

The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.

“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”

Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”

Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.

For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”

As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.

For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
 

Additional research

In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.

She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.

Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”

However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”

Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”

Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.

DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.

However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”

The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.

“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”

Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”

Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.

For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”

As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.

For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
 

Additional research

In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.

She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.

Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”

However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”

Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”

Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.

DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.

However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”

The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.

“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”

Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”

Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.

For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”

As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.

For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
 

Additional research

In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.

She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.

Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”

However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”

Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”

Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Young Black sexual-minority men (YBSMM) who experience sleep disturbance at least 3-4 times a week are much more likely to miss HIV pre-exposure prophylaxis (PrEP) doses than those who rarely report sleep disturbance, according to a new study published online in the journal AIDS and Behavior.

Sleep disturbance, poor cognitive processing, and memory function deficits go hand in hand, especially among people living with HIV. 

Data have suggested that poor sleep might be an important factor in common neurocognitive complaints and overall health outcomes, especially among older adults with HIV. But few studies have examined the role that sleep quality might play in driving health behaviors around prevention and PrEP adherence, especially among YBSMM, who are at highest risk for acquiring new HIV infections.

Commonly cited reasons for suboptimal HIV prevention efforts within this population often include stigma, mistrust of the medical system, and a lack of culturally appropriate care.

“We make a lot of assumptions about young people and their brains and their ability to remember things, namely [that] they should be better than older adults at remembering to take medications,” lead study investigator Jade Pagkas-Bather, MD, an infectious disease specialist at University of Chicago Medicine, told this news organization. 

“In reality, many young people are not used to taking medications, [especially] for a disease that they do not have.”
 

Too many pills, too little sleep

The researchers examined data collected from participants in the Neighborhoods and Networks Cohort Study, Chicago, which looked at the role of social, contextual, network, and geospatial factors influencing HIV prevention and care in HIV-negative, cisgender YBSMM between 2018 and 2019. 

The investigators included 70 YBSMM participants who reported current PrEP use in the analysis. All were between the ages of 16 and 24 years, self-identified as African American or Black, were assigned male at birth, and reported at least one sexual encounter with a man or transgender woman in the previous 12 months.

Sleep was measured using the Patient Health Questionnaire-9 (PHQ-9) which includes a question on frequency of sleep disturbance (that is, trouble falling asleep, staying asleep, or sleeping too much) categorized as follows: less than 1 day (rarely or none of the time), 1-2 days (some or a little of the time), 3-4 days (occasionally or a moderate amount of time), or 5-7 days (all of the time).

Almost half (47.1%) of participants self-reported some or moderate sleep disturbance, with 8.6% having sleep disturbance all of the time. 

“One of the main findings was that poor sleep and having too many pills impacts people’s ability to remember to take their PrEP or is associated with missing PrEP doses,” explained Dr. Pagkas-Bather.

In adjusted models, YBSMM who reported moderate sleep disturbances cited having too many pills to take as the reason for missing or forgetting PrEP doses (adjusted odds ratio, 7.59; 95% confidence interval, 1.05-54.57), compared with peers who did not have sleep issues.

Depression was likewise an important factor. Participants who reported experiencing sleep disturbance all of the time and missing PrEP doses were also highly likely to be depressed (aOR, 11.30; 95% CI, 1.19-107.53).

“The PHQ-9 is a widely accepted measure looking at depression – and sleep as one symptom of depression,” explained Brooke Genkin Rogers, Ph.D., M.P.H., a research scientist and assistant professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University, Providence, R.I. 

Dr. Rogers, who was not involved in the study, noted, “Sleep disturbance is a sign of poor physical or mental health, particularly in an otherwise younger, healthier population.” But Dr. Rogers also had questions about sleep duration (that is, too short or too long) and whether or not it also played a role in poor adherence, information that was not pursued within the study. 

“As a clinician, I see quite a few people who are young Black sexual minority men who are on PrEP, or on the converse side, people living with HIV and taking medications for HIV treatment. I would posit a guess that it’s not that people are necessarily sleeping too much, but there are other sorts of factors that interfere with being able to get 8 hours of sleep a night,” explained Dr. Pagkas-Bather.

They include structural issues like greater exposure to housing instability and neighborhood safety. 

However, Dr. Pagkas-Bather pointed to an even more critical factor influencing PrEP usage and adherence, one that she refers to as “Trickle Up HIV Care.”

“We can’t just come up with interventions, drugs, and studies and say, we have all of these options, anyone who wants them, come and get them,” she said. “We really need to work very hard at educating and encouraging populations who have no high-level need for prevention and treatment.”

As a clinician who works closely with the YBSMM population, Dr. Pagkas-Bather also shared that her patients have told her that they’ve asked for PrEP and have had providers turn them down because they weren’t comfortable prescribing PrEP or made assumptions about the kind of people who are on PrEP. 

“There are sometimes assumptions made about Black men and sexual promiscuity. And the data doesn’t bear that out. It’s not that Black men are having more sex than White men or any other man; it’s that the prevalence of HIV in the Black community is higher overall relative to the population,” noted Dr. Pagkas-Bather.

“We need a nuanced approach to examining these issues ... to take a look at multiple levels of influence on folks’ health and HIV risk,” said Dr. Rogers.

Both clinicians acknowledged that creative solutions have not been exhausted. 

“There’s a lot of opportunity if we sit down with communities and share in decisions around HIV treatment and prevention ... if we tap into the wealth and knowledge of the Black communities to prevent HIV,” concluded Dr. Pagkas-Bather.

Dr. Pagkas-Bather reports that she is a Gilead Sciences HIV Research Scholar awardee. Dr. Rogers reports receiving a scientific research grant from Gilead Sciences. 

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

Young Black sexual-minority men (YBSMM) who experience sleep disturbance at least 3-4 times a week are much more likely to miss HIV pre-exposure prophylaxis (PrEP) doses than those who rarely report sleep disturbance, according to a new study published online in the journal AIDS and Behavior.

Sleep disturbance, poor cognitive processing, and memory function deficits go hand in hand, especially among people living with HIV. 

Data have suggested that poor sleep might be an important factor in common neurocognitive complaints and overall health outcomes, especially among older adults with HIV. But few studies have examined the role that sleep quality might play in driving health behaviors around prevention and PrEP adherence, especially among YBSMM, who are at highest risk for acquiring new HIV infections.

Commonly cited reasons for suboptimal HIV prevention efforts within this population often include stigma, mistrust of the medical system, and a lack of culturally appropriate care.

“We make a lot of assumptions about young people and their brains and their ability to remember things, namely [that] they should be better than older adults at remembering to take medications,” lead study investigator Jade Pagkas-Bather, MD, an infectious disease specialist at University of Chicago Medicine, told this news organization. 

“In reality, many young people are not used to taking medications, [especially] for a disease that they do not have.”
 

Too many pills, too little sleep

The researchers examined data collected from participants in the Neighborhoods and Networks Cohort Study, Chicago, which looked at the role of social, contextual, network, and geospatial factors influencing HIV prevention and care in HIV-negative, cisgender YBSMM between 2018 and 2019. 

The investigators included 70 YBSMM participants who reported current PrEP use in the analysis. All were between the ages of 16 and 24 years, self-identified as African American or Black, were assigned male at birth, and reported at least one sexual encounter with a man or transgender woman in the previous 12 months.

Sleep was measured using the Patient Health Questionnaire-9 (PHQ-9) which includes a question on frequency of sleep disturbance (that is, trouble falling asleep, staying asleep, or sleeping too much) categorized as follows: less than 1 day (rarely or none of the time), 1-2 days (some or a little of the time), 3-4 days (occasionally or a moderate amount of time), or 5-7 days (all of the time).

Almost half (47.1%) of participants self-reported some or moderate sleep disturbance, with 8.6% having sleep disturbance all of the time. 

“One of the main findings was that poor sleep and having too many pills impacts people’s ability to remember to take their PrEP or is associated with missing PrEP doses,” explained Dr. Pagkas-Bather.

In adjusted models, YBSMM who reported moderate sleep disturbances cited having too many pills to take as the reason for missing or forgetting PrEP doses (adjusted odds ratio, 7.59; 95% confidence interval, 1.05-54.57), compared with peers who did not have sleep issues.

Depression was likewise an important factor. Participants who reported experiencing sleep disturbance all of the time and missing PrEP doses were also highly likely to be depressed (aOR, 11.30; 95% CI, 1.19-107.53).

“The PHQ-9 is a widely accepted measure looking at depression – and sleep as one symptom of depression,” explained Brooke Genkin Rogers, Ph.D., M.P.H., a research scientist and assistant professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University, Providence, R.I. 

Dr. Rogers, who was not involved in the study, noted, “Sleep disturbance is a sign of poor physical or mental health, particularly in an otherwise younger, healthier population.” But Dr. Rogers also had questions about sleep duration (that is, too short or too long) and whether or not it also played a role in poor adherence, information that was not pursued within the study. 

“As a clinician, I see quite a few people who are young Black sexual minority men who are on PrEP, or on the converse side, people living with HIV and taking medications for HIV treatment. I would posit a guess that it’s not that people are necessarily sleeping too much, but there are other sorts of factors that interfere with being able to get 8 hours of sleep a night,” explained Dr. Pagkas-Bather.

They include structural issues like greater exposure to housing instability and neighborhood safety. 

However, Dr. Pagkas-Bather pointed to an even more critical factor influencing PrEP usage and adherence, one that she refers to as “Trickle Up HIV Care.”

“We can’t just come up with interventions, drugs, and studies and say, we have all of these options, anyone who wants them, come and get them,” she said. “We really need to work very hard at educating and encouraging populations who have no high-level need for prevention and treatment.”

As a clinician who works closely with the YBSMM population, Dr. Pagkas-Bather also shared that her patients have told her that they’ve asked for PrEP and have had providers turn them down because they weren’t comfortable prescribing PrEP or made assumptions about the kind of people who are on PrEP. 

“There are sometimes assumptions made about Black men and sexual promiscuity. And the data doesn’t bear that out. It’s not that Black men are having more sex than White men or any other man; it’s that the prevalence of HIV in the Black community is higher overall relative to the population,” noted Dr. Pagkas-Bather.

“We need a nuanced approach to examining these issues ... to take a look at multiple levels of influence on folks’ health and HIV risk,” said Dr. Rogers.

Both clinicians acknowledged that creative solutions have not been exhausted. 

“There’s a lot of opportunity if we sit down with communities and share in decisions around HIV treatment and prevention ... if we tap into the wealth and knowledge of the Black communities to prevent HIV,” concluded Dr. Pagkas-Bather.

Dr. Pagkas-Bather reports that she is a Gilead Sciences HIV Research Scholar awardee. Dr. Rogers reports receiving a scientific research grant from Gilead Sciences. 

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

Young Black sexual-minority men (YBSMM) who experience sleep disturbance at least 3-4 times a week are much more likely to miss HIV pre-exposure prophylaxis (PrEP) doses than those who rarely report sleep disturbance, according to a new study published online in the journal AIDS and Behavior.

Sleep disturbance, poor cognitive processing, and memory function deficits go hand in hand, especially among people living with HIV. 

Data have suggested that poor sleep might be an important factor in common neurocognitive complaints and overall health outcomes, especially among older adults with HIV. But few studies have examined the role that sleep quality might play in driving health behaviors around prevention and PrEP adherence, especially among YBSMM, who are at highest risk for acquiring new HIV infections.

Commonly cited reasons for suboptimal HIV prevention efforts within this population often include stigma, mistrust of the medical system, and a lack of culturally appropriate care.

“We make a lot of assumptions about young people and their brains and their ability to remember things, namely [that] they should be better than older adults at remembering to take medications,” lead study investigator Jade Pagkas-Bather, MD, an infectious disease specialist at University of Chicago Medicine, told this news organization. 

“In reality, many young people are not used to taking medications, [especially] for a disease that they do not have.”
 

Too many pills, too little sleep

The researchers examined data collected from participants in the Neighborhoods and Networks Cohort Study, Chicago, which looked at the role of social, contextual, network, and geospatial factors influencing HIV prevention and care in HIV-negative, cisgender YBSMM between 2018 and 2019. 

The investigators included 70 YBSMM participants who reported current PrEP use in the analysis. All were between the ages of 16 and 24 years, self-identified as African American or Black, were assigned male at birth, and reported at least one sexual encounter with a man or transgender woman in the previous 12 months.

Sleep was measured using the Patient Health Questionnaire-9 (PHQ-9) which includes a question on frequency of sleep disturbance (that is, trouble falling asleep, staying asleep, or sleeping too much) categorized as follows: less than 1 day (rarely or none of the time), 1-2 days (some or a little of the time), 3-4 days (occasionally or a moderate amount of time), or 5-7 days (all of the time).

Almost half (47.1%) of participants self-reported some or moderate sleep disturbance, with 8.6% having sleep disturbance all of the time. 

“One of the main findings was that poor sleep and having too many pills impacts people’s ability to remember to take their PrEP or is associated with missing PrEP doses,” explained Dr. Pagkas-Bather.

In adjusted models, YBSMM who reported moderate sleep disturbances cited having too many pills to take as the reason for missing or forgetting PrEP doses (adjusted odds ratio, 7.59; 95% confidence interval, 1.05-54.57), compared with peers who did not have sleep issues.

Depression was likewise an important factor. Participants who reported experiencing sleep disturbance all of the time and missing PrEP doses were also highly likely to be depressed (aOR, 11.30; 95% CI, 1.19-107.53).

“The PHQ-9 is a widely accepted measure looking at depression – and sleep as one symptom of depression,” explained Brooke Genkin Rogers, Ph.D., M.P.H., a research scientist and assistant professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University, Providence, R.I. 

Dr. Rogers, who was not involved in the study, noted, “Sleep disturbance is a sign of poor physical or mental health, particularly in an otherwise younger, healthier population.” But Dr. Rogers also had questions about sleep duration (that is, too short or too long) and whether or not it also played a role in poor adherence, information that was not pursued within the study. 

“As a clinician, I see quite a few people who are young Black sexual minority men who are on PrEP, or on the converse side, people living with HIV and taking medications for HIV treatment. I would posit a guess that it’s not that people are necessarily sleeping too much, but there are other sorts of factors that interfere with being able to get 8 hours of sleep a night,” explained Dr. Pagkas-Bather.

They include structural issues like greater exposure to housing instability and neighborhood safety. 

However, Dr. Pagkas-Bather pointed to an even more critical factor influencing PrEP usage and adherence, one that she refers to as “Trickle Up HIV Care.”

“We can’t just come up with interventions, drugs, and studies and say, we have all of these options, anyone who wants them, come and get them,” she said. “We really need to work very hard at educating and encouraging populations who have no high-level need for prevention and treatment.”

As a clinician who works closely with the YBSMM population, Dr. Pagkas-Bather also shared that her patients have told her that they’ve asked for PrEP and have had providers turn them down because they weren’t comfortable prescribing PrEP or made assumptions about the kind of people who are on PrEP. 

“There are sometimes assumptions made about Black men and sexual promiscuity. And the data doesn’t bear that out. It’s not that Black men are having more sex than White men or any other man; it’s that the prevalence of HIV in the Black community is higher overall relative to the population,” noted Dr. Pagkas-Bather.

“We need a nuanced approach to examining these issues ... to take a look at multiple levels of influence on folks’ health and HIV risk,” said Dr. Rogers.

Both clinicians acknowledged that creative solutions have not been exhausted. 

“There’s a lot of opportunity if we sit down with communities and share in decisions around HIV treatment and prevention ... if we tap into the wealth and knowledge of the Black communities to prevent HIV,” concluded Dr. Pagkas-Bather.

Dr. Pagkas-Bather reports that she is a Gilead Sciences HIV Research Scholar awardee. Dr. Rogers reports receiving a scientific research grant from Gilead Sciences. 

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