MDedge Neurology

A new study provides more evidence that influenza vaccination may help protect older adults against Alzheimer’s disease (AD).

In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.

“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.

The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.

The latest study was published online in the Journal of Alzheimer’s Disease.
 

40% lower risk

Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.

However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.

Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.

The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.

During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.

The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
 

Mechanism unclear

“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.

“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.

It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.

“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
 

Alzheimer’s expert weighs in

Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.

“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.

“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.

“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.

The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.

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

A new study provides more evidence that influenza vaccination may help protect older adults against Alzheimer’s disease (AD).

In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.

“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.

The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.

The latest study was published online in the Journal of Alzheimer’s Disease.
 

40% lower risk

Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.

However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.

Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.

The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.

During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.

The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
 

Mechanism unclear

“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.

“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.

It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.

“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
 

Alzheimer’s expert weighs in

Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.

“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.

“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.

“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.

The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.

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

A new study provides more evidence that influenza vaccination may help protect older adults against Alzheimer’s disease (AD).

In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.

“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.

The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.

The latest study was published online in the Journal of Alzheimer’s Disease.
 

40% lower risk

Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.

However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.

Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.

The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.

During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.

The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
 

Mechanism unclear

“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.

“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.

It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.

“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
 

Alzheimer’s expert weighs in

Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.

“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.

“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.

“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.

The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

The U.S. Food and Drug Administration has unveiled a 5-year strategy aimed at improving and extending the lives of people with rare neurodegenerative diseases.

The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.

“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.

“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.

“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
 

Blueprint to ‘aggressively’ move forward

The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.

The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.

Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.

The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.

The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.

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

The U.S. Food and Drug Administration has unveiled a 5-year strategy aimed at improving and extending the lives of people with rare neurodegenerative diseases.

The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.

“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.

“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.

“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
 

Blueprint to ‘aggressively’ move forward

The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.

The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.

Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.

The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.

The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.

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

The U.S. Food and Drug Administration has unveiled a 5-year strategy aimed at improving and extending the lives of people with rare neurodegenerative diseases.

The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.

“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.

“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.

“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
 

Blueprint to ‘aggressively’ move forward

The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.

The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.

Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.

The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.

The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.

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

I’m not hiding anything.

Occasionally I deal with patients and families who seem to think I have some miracle cure for a condition that I’m not telling them about.

I promise, I don’t work that way. Besides the obvious ethical issues, why would I? What could I possibly gain from doing that?

The trouble is that people are blanketed by news headlines, some reputable and some not, about a research study suggesting a new direction in treatment, or that a new drug in development has promise. Often these stories are forwarded to them by well-meaning relatives and friends, or just show up in their social media feed.

While some of these findings may actually lead somewhere, the vast majority don’t. In my career I’ve seen statins touted as potential treatments for MS and Alzheimer’s disease, and vilified as causes of dementia and peripheral neuropathy, all disproved or (to date) still up in the air.

But nonmedical people don’t understand that. It made the news, so it must mean something. I have no problem trying to explain this to them, but it’s never easy.

It’s even harder to explain to the ones who’ve already purchased a costly over-the-counter placebo for such a condition that they wasted their money.

We live in a world of amazing technological achievements, but that doesn’t mean all diseases have been cured and problems fixed. Far from it.

New discoveries are made, but a lot of times it’s a very slow journey to find the solution. One discovery may not lead to THE answer, but hopefully will get you closer to it.

That generally doesn’t happen overnight. The mathematical problem of Goldbach’s Conjecture has been around since 1742 and still hasn’t been definitively answered.

Medicine isn’t math, either. The people and families dealing with these conditions want answers. I don’t blame them. So do I. Believe me, there would be nothing that would bring me more joy as a doctor than to be able to give someone with a serious diagnosis the comfort that comes with saying it’s also curable.

I never have, and never would, withhold such a thing from a patient. Ever. I just wish some of them would believe me when I say that.

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

I’m not hiding anything.

Occasionally I deal with patients and families who seem to think I have some miracle cure for a condition that I’m not telling them about.

I promise, I don’t work that way. Besides the obvious ethical issues, why would I? What could I possibly gain from doing that?

The trouble is that people are blanketed by news headlines, some reputable and some not, about a research study suggesting a new direction in treatment, or that a new drug in development has promise. Often these stories are forwarded to them by well-meaning relatives and friends, or just show up in their social media feed.

While some of these findings may actually lead somewhere, the vast majority don’t. In my career I’ve seen statins touted as potential treatments for MS and Alzheimer’s disease, and vilified as causes of dementia and peripheral neuropathy, all disproved or (to date) still up in the air.

But nonmedical people don’t understand that. It made the news, so it must mean something. I have no problem trying to explain this to them, but it’s never easy.

It’s even harder to explain to the ones who’ve already purchased a costly over-the-counter placebo for such a condition that they wasted their money.

We live in a world of amazing technological achievements, but that doesn’t mean all diseases have been cured and problems fixed. Far from it.

New discoveries are made, but a lot of times it’s a very slow journey to find the solution. One discovery may not lead to THE answer, but hopefully will get you closer to it.

That generally doesn’t happen overnight. The mathematical problem of Goldbach’s Conjecture has been around since 1742 and still hasn’t been definitively answered.

Medicine isn’t math, either. The people and families dealing with these conditions want answers. I don’t blame them. So do I. Believe me, there would be nothing that would bring me more joy as a doctor than to be able to give someone with a serious diagnosis the comfort that comes with saying it’s also curable.

I never have, and never would, withhold such a thing from a patient. Ever. I just wish some of them would believe me when I say that.

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

I’m not hiding anything.

Occasionally I deal with patients and families who seem to think I have some miracle cure for a condition that I’m not telling them about.

I promise, I don’t work that way. Besides the obvious ethical issues, why would I? What could I possibly gain from doing that?

The trouble is that people are blanketed by news headlines, some reputable and some not, about a research study suggesting a new direction in treatment, or that a new drug in development has promise. Often these stories are forwarded to them by well-meaning relatives and friends, or just show up in their social media feed.

While some of these findings may actually lead somewhere, the vast majority don’t. In my career I’ve seen statins touted as potential treatments for MS and Alzheimer’s disease, and vilified as causes of dementia and peripheral neuropathy, all disproved or (to date) still up in the air.

But nonmedical people don’t understand that. It made the news, so it must mean something. I have no problem trying to explain this to them, but it’s never easy.

It’s even harder to explain to the ones who’ve already purchased a costly over-the-counter placebo for such a condition that they wasted their money.

We live in a world of amazing technological achievements, but that doesn’t mean all diseases have been cured and problems fixed. Far from it.

New discoveries are made, but a lot of times it’s a very slow journey to find the solution. One discovery may not lead to THE answer, but hopefully will get you closer to it.

That generally doesn’t happen overnight. The mathematical problem of Goldbach’s Conjecture has been around since 1742 and still hasn’t been definitively answered.

Medicine isn’t math, either. The people and families dealing with these conditions want answers. I don’t blame them. So do I. Believe me, there would be nothing that would bring me more joy as a doctor than to be able to give someone with a serious diagnosis the comfort that comes with saying it’s also curable.

I never have, and never would, withhold such a thing from a patient. Ever. I just wish some of them would believe me when I say that.

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

DENVER – A new study finds that females with male twins are more likely to suffer from migraines without aura than are those with female twins, even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.

The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
 

More than genetics

The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.

Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.

To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.

One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.

Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.

“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
 

Probing the migraine gender gap

Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”

As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.

“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”

Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”

As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”

The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.

DENVER – A new study finds that females with male twins are more likely to suffer from migraines without aura than are those with female twins, even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.

The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
 

More than genetics

The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.

Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.

To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.

One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.

Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.

“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
 

Probing the migraine gender gap

Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”

As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.

“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”

Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”

As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”

The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.

DENVER – A new study finds that females with male twins are more likely to suffer from migraines without aura than are those with female twins, even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.

The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
 

More than genetics

The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.

Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.

To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.

One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.

Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.

“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
 

Probing the migraine gender gap

Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”

As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.

“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”

Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”

As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”

The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.

Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.

Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.

“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.

tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.

The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
 

First study of its kind

Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.

Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.

“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.

Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.

The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.

Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.

In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.

A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.

The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.

The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.

The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.

The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.

Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.

This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.

Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
 

Encouraging results offer new hope

Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.

“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”

“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.

“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.

“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.

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

Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.

Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.

“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.

tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.

The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
 

First study of its kind

Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.

Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.

“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.

Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.

The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.

Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.

In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.

A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.

The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.

The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.

The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.

The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.

Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.

This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.

Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
 

Encouraging results offer new hope

Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.

“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”

“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.

“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.

“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.

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

Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.

Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.

“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.

tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.

The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
 

First study of its kind

Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.

Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.

“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.

Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.

The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.

Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.

In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.

A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.

The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.

The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.

The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.

The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.

Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.

This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.

Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
 

Encouraging results offer new hope

Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.

“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”

“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.

“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.

“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.

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

Acupuncture deep needling provides significant, long-term relief from chronic tension type headache (TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.

At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.

“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.

The findings were published online in Neurology.
 

Deqi sensation key

TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.

Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.

To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.

The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.

The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.

At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).

Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.

Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.

Only four patients reported adverse effects, all of which were mild and none requiring treatment.

Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.

“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
 

Deeper understanding?

Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.

“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.

However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.

“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.

The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.

“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.

Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.

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

Acupuncture deep needling provides significant, long-term relief from chronic tension type headache (TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.

At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.

“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.

The findings were published online in Neurology.
 

Deqi sensation key

TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.

Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.

To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.

The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.

The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.

At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).

Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.

Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.

Only four patients reported adverse effects, all of which were mild and none requiring treatment.

Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.

“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
 

Deeper understanding?

Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.

“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.

However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.

“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.

The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.

“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.

Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.

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

Acupuncture deep needling provides significant, long-term relief from chronic tension type headache (TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.

At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.

“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.

The findings were published online in Neurology.
 

Deqi sensation key

TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.

Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.

To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.

The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.

The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.

At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).

Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.

Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.

Only four patients reported adverse effects, all of which were mild and none requiring treatment.

Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.

“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
 

Deeper understanding?

Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.

“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.

However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.

“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.

The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.

“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.

Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.

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

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

It took Michael Golden, MD, 5 years to decide to switch to a concierge practice, in which patients pay a monthly or annual fee for more personalized care. Dr. Golden, an internist in Beverly, Mass., changed course in 2021, during the COVID-19 pandemic.

“I’m not sure why I hesitated for so long,” said Dr. Golden.

Once they take the plunge into concierge practice or direct primary care (DPC) – a related form of retainer-based practice – many doctors are delighted with the change. But taking the plunge is a big step that they sometimes put off for years.

“The main factors for waiting are fear, uncertainty, and doubt,” said Leigh “Jack” Forbush, DO, a family physician who runs a DPC practice in Hampden, Maine, and mentors doctors contemplating the switch.

According to Dr. Forbush, the critical questions doctors ask themselves are, “Will I be able to find enough paying patients?” and – in the case of DPC practices, which cancel insurance – “Can I live without the money I get from insurers?”

Terry Bauer, CEO of Specialdocs Consultants in Highland Park, Ill., which helps doctors move to a concierge practice, said many of his clients put off the decision for as long as 15 years.

“Clients became progressively worn out – or even burnt out – by the demands of fee-for-service medicine,” said Dr. Bauer. “For women, the tipping point can be when their kids ask, ‘Mom, do you like your job better than me?’ For men, it may be more about feeling tired and unsatisfied with their work.”

But once these doctors make the switch, it’s with all their heart. “A client recently told me that if he couldn’t open a concierge practice, he might have to quit medicine,” Dr. Bauer said. “And he’s only 51.”
 

Few doctors regret switching

A 2020 survey of DPC physicians for the Society of Actuaries found that 99% reported having better or much better overall personal and professional satisfaction.

Retainer-based physicians report feeling much more relaxed after they start a concierge practice. On many workdays, Dr. Golden takes a walk on a trail in the woods behind his office. “That’s something I couldn’t do before,” he said. “And I go to my kids’ soccer games. I’m able to be present in their lives now.”

Since retainer-based doctors have markedly fewer patients, they can form personal relationships with each one. When Dr. Golden switched, he “went from having a couple of thousand patients to a few hundred,” he said.

“I know each patient now,” said Dorothy Cohen Serna, MD, an internist in Cypress, Tex., who moved to concierge in 2017. “I don’t need to look at their chart to know who they are.”

Dr. Serna said patients’ close relationship with her helped them get through the worst months of the pandemic. “They were scared, depressed, and concerned, and they needed a lot of individual attention,” she said.

Because they see fewer patients, concierge doctors can lengthen appointment times to about 30 minutes – or longer, if necessary. They no longer have a problem answering patients’ “doorknob questions” – wholly new concerns brought up at the end of the visit.

“The appointment might be for a sprained ankle, and then the patient might mention they haven’t been sleeping well,” Dr. Golden said. “I have time to talk about that without worrying that my schedule is getting backed up.”
 

Why patients sign up

Retainer-based practices are still an exotic concept in many areas, but patients are beginning to understand the value, said Shalini Kaneriya, MD, an internist in Herndon, Va,, who switched her practice to concierge in 2018.

Several hundred patients followed her into her new practice because “people realized their care would be better if they had a concierge doctor,” she said. Two years ago, partly because of growing demand, she recruited another physician as an associate.

“People want a relationship with their doctor,” Dr. Serna added. “It’s hard to provide that in a regular practice.”

Todd Granger, MD, an internist who opened a DPC practice in Chapel Hill, N.C., in 2016, said new patients often mention feeling rushed through appointments with their previous doctors. Also, “it’s hard to get to see a doctor around here.”

Scott Bernstein, MD, an internist who runs a DPC practice in Scottsdale, Ariz., said he can arrange to have patients see specialists much faster than if they try to make appointments on their own. “I personally call specialists and then prep my patients on how to deal with the appointment,” he said.

Retainer-based practices tend to have a greater number of older and chronically ill patients, but they also attract patients who need less care. “The healthier patients find value in our proactive approach to prevention and wellness,” Dr. Serna said.

Some concierge physicians charge higher fees to patients who need more care, but many decide this is too complicated and charge everyone the same fee. Dr. Granger said he initially had a variable fee schedule, but when some lower-paying patients began to need more visits, he had to consider charging them extra. “Now I basically have just one fee,” he said.
 

Not a good fit for many physicians

Dr. Bauer said a lot of physicians are interested in retainer-based practice, but many of them might not make the income they had hoped for. Specialdocs interviews physicians who inquire about the model and ultimately doesn’t contract with 80% of them, Dr. Bauer said.

To be able to sign up and retain enough patients, the doctor’s attitude is important. “You have to be driven by the desire to go deep with patients -- to work hard with them and deal with their issues,” said Erika Bliss, MD, who runs a DPC practice in Seattle.

Dr. Bernstein said retainer-based physicians have to be interested in lifestyle issues, such as diet, exercise, and sleep. “I spend a lot of time dealing with issues like how to incorporate physical activity into daily routines,” he said. “Some doctors wouldn’t enjoy doing that.”

Also, concierge physicians have to be available all the time. “Patients have my cell phone number,” Dr. Granger said. “They could call in the middle of the night, but they usually don’t.”

To ensure that they get some time off, many concierge physicians have partners. Dr. Bernstein and another DPC doctor maintain separate practices but cover for each other. Each takes every other weekend off plus 6 weeks every year.
 

Can you attract enough patients?

A key challenge is finding enough patients to sustain a concierge practice. Planning the switch involves setting a target number of patients needed for the doctor to make a decent income after paying practice expenses. For example, a doctor charging $300 a month to 250 patients would gross $900,000 per year, and then pay practice expenses from that.

Attracting the target number of patients can take months or even years. After almost 6 years, Dr. Granger said, he has around 240 patients ― well below his target number of 440.

Partly because the practice model is not well known in North Carolina, Dr. Granger set his fee very low, at $60 a month, then raised it to $75. That means his practice has been grossing just $216,000 a year. But he is not about to give up. He plans to raise his fee in July and hopes that word of mouth will add more patients.

If physicians cannot earn enough in their concierge practice, Dr. Bauer said, they may moonlight at a local hospital or work for a telemedicine company. He hasn’t heard of physicians closing their concierge practice and returning to their previous practice model. “They didn’t like what they were doing before,” he said.
 

Opening up to lower-income patients

Dr. Granger’s $75 monthly fee is an example of how retainer-based medicine has transformed itself from a gold-plated service for rich people to a service that middle-class and even lower-income people can afford. DPC practices like Dr. Granger’s have dramatically lowered expenses by cutting out the need to bill insurance companies. Some DPC practices further reduce expenses by not having any staff and by renting out office space.

Dr. Forbush’s Pine Tree State patients are mostly blue-collar workers – electricians, plumbers, people who work in small businesses. He charges them $150 a month, which most patients who don’t have health insurance can afford. He said three-quarters of his patients lack health insurance, although some have back-up finances, such as health savings accounts.

Since his patients have to pay out of pocket for tests and specialists, Dr. Forbush keeps referrals in check by handling many problems himself. “Since I have more time to spend with the patient, I can often work out issues that other doctors might ask specialists to deal with,” he said.

He has learned some dermatologic procedures. “There are plenty of things I can handle on my own,” he said.

Dr. Granger adds that by examining patients during longer appointments, expensive diagnostic exams are not always necessary.
 

The challenges for this model

Many experts warn that retainer-based practices won’t work for doctors who want to leave employment or for doctors fresh out of residency. Not having your own patients to bring into the new practice is a big minus, because this is the best way to start the new practice.

Still, there are other ways to find patients. Dr. Bauer said physicians can advertise online, make themselves known by giving speeches in the community, or contract with small employers to treat their workers.

Dr. Bauer said some of his clients were employed physicians, and he thinks they will become a bigger factor now that fewer doctors remain in private practice. The chief barrier for employed physicians is the restrictive covenant that prevents them from setting up a practice nearby. But Dr. Bauer said some employers are willing to waive restrictive covenants for retainer-based doctors.

New physicians are also adopting the concierge model. Dr. Forbush said physicians straight out of residency have set up DPC practices in Maine. They signed up patients for their new practices even before they graduated, he said.

Retainer-based medicine is still mainly limited to primary care physicians, but according to Dr. Bauer, it can also work for specialists who have long-term relationships with patients, such as cardiologists, ob.gyns., rheumatologists, neurologists, and endocrinologists.
 

No going back

Most doctors who make the switch to retainer-based practice understand that there’s likely no going back. When Dr. Bernstein switched, he announced the change to patients and canceled insurance contracts. “It was make or break,” he said. “I had no parachute.”

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

It took Michael Golden, MD, 5 years to decide to switch to a concierge practice, in which patients pay a monthly or annual fee for more personalized care. Dr. Golden, an internist in Beverly, Mass., changed course in 2021, during the COVID-19 pandemic.

“I’m not sure why I hesitated for so long,” said Dr. Golden.

Once they take the plunge into concierge practice or direct primary care (DPC) – a related form of retainer-based practice – many doctors are delighted with the change. But taking the plunge is a big step that they sometimes put off for years.

“The main factors for waiting are fear, uncertainty, and doubt,” said Leigh “Jack” Forbush, DO, a family physician who runs a DPC practice in Hampden, Maine, and mentors doctors contemplating the switch.

According to Dr. Forbush, the critical questions doctors ask themselves are, “Will I be able to find enough paying patients?” and – in the case of DPC practices, which cancel insurance – “Can I live without the money I get from insurers?”

Terry Bauer, CEO of Specialdocs Consultants in Highland Park, Ill., which helps doctors move to a concierge practice, said many of his clients put off the decision for as long as 15 years.

“Clients became progressively worn out – or even burnt out – by the demands of fee-for-service medicine,” said Dr. Bauer. “For women, the tipping point can be when their kids ask, ‘Mom, do you like your job better than me?’ For men, it may be more about feeling tired and unsatisfied with their work.”

But once these doctors make the switch, it’s with all their heart. “A client recently told me that if he couldn’t open a concierge practice, he might have to quit medicine,” Dr. Bauer said. “And he’s only 51.”
 

Few doctors regret switching

A 2020 survey of DPC physicians for the Society of Actuaries found that 99% reported having better or much better overall personal and professional satisfaction.

Retainer-based physicians report feeling much more relaxed after they start a concierge practice. On many workdays, Dr. Golden takes a walk on a trail in the woods behind his office. “That’s something I couldn’t do before,” he said. “And I go to my kids’ soccer games. I’m able to be present in their lives now.”

Since retainer-based doctors have markedly fewer patients, they can form personal relationships with each one. When Dr. Golden switched, he “went from having a couple of thousand patients to a few hundred,” he said.

“I know each patient now,” said Dorothy Cohen Serna, MD, an internist in Cypress, Tex., who moved to concierge in 2017. “I don’t need to look at their chart to know who they are.”

Dr. Serna said patients’ close relationship with her helped them get through the worst months of the pandemic. “They were scared, depressed, and concerned, and they needed a lot of individual attention,” she said.

Because they see fewer patients, concierge doctors can lengthen appointment times to about 30 minutes – or longer, if necessary. They no longer have a problem answering patients’ “doorknob questions” – wholly new concerns brought up at the end of the visit.

“The appointment might be for a sprained ankle, and then the patient might mention they haven’t been sleeping well,” Dr. Golden said. “I have time to talk about that without worrying that my schedule is getting backed up.”
 

Why patients sign up

Retainer-based practices are still an exotic concept in many areas, but patients are beginning to understand the value, said Shalini Kaneriya, MD, an internist in Herndon, Va,, who switched her practice to concierge in 2018.

Several hundred patients followed her into her new practice because “people realized their care would be better if they had a concierge doctor,” she said. Two years ago, partly because of growing demand, she recruited another physician as an associate.

“People want a relationship with their doctor,” Dr. Serna added. “It’s hard to provide that in a regular practice.”

Todd Granger, MD, an internist who opened a DPC practice in Chapel Hill, N.C., in 2016, said new patients often mention feeling rushed through appointments with their previous doctors. Also, “it’s hard to get to see a doctor around here.”

Scott Bernstein, MD, an internist who runs a DPC practice in Scottsdale, Ariz., said he can arrange to have patients see specialists much faster than if they try to make appointments on their own. “I personally call specialists and then prep my patients on how to deal with the appointment,” he said.

Retainer-based practices tend to have a greater number of older and chronically ill patients, but they also attract patients who need less care. “The healthier patients find value in our proactive approach to prevention and wellness,” Dr. Serna said.

Some concierge physicians charge higher fees to patients who need more care, but many decide this is too complicated and charge everyone the same fee. Dr. Granger said he initially had a variable fee schedule, but when some lower-paying patients began to need more visits, he had to consider charging them extra. “Now I basically have just one fee,” he said.
 

Not a good fit for many physicians

Dr. Bauer said a lot of physicians are interested in retainer-based practice, but many of them might not make the income they had hoped for. Specialdocs interviews physicians who inquire about the model and ultimately doesn’t contract with 80% of them, Dr. Bauer said.

To be able to sign up and retain enough patients, the doctor’s attitude is important. “You have to be driven by the desire to go deep with patients -- to work hard with them and deal with their issues,” said Erika Bliss, MD, who runs a DPC practice in Seattle.

Dr. Bernstein said retainer-based physicians have to be interested in lifestyle issues, such as diet, exercise, and sleep. “I spend a lot of time dealing with issues like how to incorporate physical activity into daily routines,” he said. “Some doctors wouldn’t enjoy doing that.”

Also, concierge physicians have to be available all the time. “Patients have my cell phone number,” Dr. Granger said. “They could call in the middle of the night, but they usually don’t.”

To ensure that they get some time off, many concierge physicians have partners. Dr. Bernstein and another DPC doctor maintain separate practices but cover for each other. Each takes every other weekend off plus 6 weeks every year.
 

Can you attract enough patients?

A key challenge is finding enough patients to sustain a concierge practice. Planning the switch involves setting a target number of patients needed for the doctor to make a decent income after paying practice expenses. For example, a doctor charging $300 a month to 250 patients would gross $900,000 per year, and then pay practice expenses from that.

Attracting the target number of patients can take months or even years. After almost 6 years, Dr. Granger said, he has around 240 patients ― well below his target number of 440.

Partly because the practice model is not well known in North Carolina, Dr. Granger set his fee very low, at $60 a month, then raised it to $75. That means his practice has been grossing just $216,000 a year. But he is not about to give up. He plans to raise his fee in July and hopes that word of mouth will add more patients.

If physicians cannot earn enough in their concierge practice, Dr. Bauer said, they may moonlight at a local hospital or work for a telemedicine company. He hasn’t heard of physicians closing their concierge practice and returning to their previous practice model. “They didn’t like what they were doing before,” he said.
 

Opening up to lower-income patients

Dr. Granger’s $75 monthly fee is an example of how retainer-based medicine has transformed itself from a gold-plated service for rich people to a service that middle-class and even lower-income people can afford. DPC practices like Dr. Granger’s have dramatically lowered expenses by cutting out the need to bill insurance companies. Some DPC practices further reduce expenses by not having any staff and by renting out office space.

Dr. Forbush’s Pine Tree State patients are mostly blue-collar workers – electricians, plumbers, people who work in small businesses. He charges them $150 a month, which most patients who don’t have health insurance can afford. He said three-quarters of his patients lack health insurance, although some have back-up finances, such as health savings accounts.

Since his patients have to pay out of pocket for tests and specialists, Dr. Forbush keeps referrals in check by handling many problems himself. “Since I have more time to spend with the patient, I can often work out issues that other doctors might ask specialists to deal with,” he said.

He has learned some dermatologic procedures. “There are plenty of things I can handle on my own,” he said.

Dr. Granger adds that by examining patients during longer appointments, expensive diagnostic exams are not always necessary.
 

The challenges for this model

Many experts warn that retainer-based practices won’t work for doctors who want to leave employment or for doctors fresh out of residency. Not having your own patients to bring into the new practice is a big minus, because this is the best way to start the new practice.

Still, there are other ways to find patients. Dr. Bauer said physicians can advertise online, make themselves known by giving speeches in the community, or contract with small employers to treat their workers.

Dr. Bauer said some of his clients were employed physicians, and he thinks they will become a bigger factor now that fewer doctors remain in private practice. The chief barrier for employed physicians is the restrictive covenant that prevents them from setting up a practice nearby. But Dr. Bauer said some employers are willing to waive restrictive covenants for retainer-based doctors.

New physicians are also adopting the concierge model. Dr. Forbush said physicians straight out of residency have set up DPC practices in Maine. They signed up patients for their new practices even before they graduated, he said.

Retainer-based medicine is still mainly limited to primary care physicians, but according to Dr. Bauer, it can also work for specialists who have long-term relationships with patients, such as cardiologists, ob.gyns., rheumatologists, neurologists, and endocrinologists.
 

No going back

Most doctors who make the switch to retainer-based practice understand that there’s likely no going back. When Dr. Bernstein switched, he announced the change to patients and canceled insurance contracts. “It was make or break,” he said. “I had no parachute.”

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

It took Michael Golden, MD, 5 years to decide to switch to a concierge practice, in which patients pay a monthly or annual fee for more personalized care. Dr. Golden, an internist in Beverly, Mass., changed course in 2021, during the COVID-19 pandemic.

“I’m not sure why I hesitated for so long,” said Dr. Golden.

Once they take the plunge into concierge practice or direct primary care (DPC) – a related form of retainer-based practice – many doctors are delighted with the change. But taking the plunge is a big step that they sometimes put off for years.

“The main factors for waiting are fear, uncertainty, and doubt,” said Leigh “Jack” Forbush, DO, a family physician who runs a DPC practice in Hampden, Maine, and mentors doctors contemplating the switch.

According to Dr. Forbush, the critical questions doctors ask themselves are, “Will I be able to find enough paying patients?” and – in the case of DPC practices, which cancel insurance – “Can I live without the money I get from insurers?”

Terry Bauer, CEO of Specialdocs Consultants in Highland Park, Ill., which helps doctors move to a concierge practice, said many of his clients put off the decision for as long as 15 years.

“Clients became progressively worn out – or even burnt out – by the demands of fee-for-service medicine,” said Dr. Bauer. “For women, the tipping point can be when their kids ask, ‘Mom, do you like your job better than me?’ For men, it may be more about feeling tired and unsatisfied with their work.”

But once these doctors make the switch, it’s with all their heart. “A client recently told me that if he couldn’t open a concierge practice, he might have to quit medicine,” Dr. Bauer said. “And he’s only 51.”
 

Few doctors regret switching

A 2020 survey of DPC physicians for the Society of Actuaries found that 99% reported having better or much better overall personal and professional satisfaction.

Retainer-based physicians report feeling much more relaxed after they start a concierge practice. On many workdays, Dr. Golden takes a walk on a trail in the woods behind his office. “That’s something I couldn’t do before,” he said. “And I go to my kids’ soccer games. I’m able to be present in their lives now.”

Since retainer-based doctors have markedly fewer patients, they can form personal relationships with each one. When Dr. Golden switched, he “went from having a couple of thousand patients to a few hundred,” he said.

“I know each patient now,” said Dorothy Cohen Serna, MD, an internist in Cypress, Tex., who moved to concierge in 2017. “I don’t need to look at their chart to know who they are.”

Dr. Serna said patients’ close relationship with her helped them get through the worst months of the pandemic. “They were scared, depressed, and concerned, and they needed a lot of individual attention,” she said.

Because they see fewer patients, concierge doctors can lengthen appointment times to about 30 minutes – or longer, if necessary. They no longer have a problem answering patients’ “doorknob questions” – wholly new concerns brought up at the end of the visit.

“The appointment might be for a sprained ankle, and then the patient might mention they haven’t been sleeping well,” Dr. Golden said. “I have time to talk about that without worrying that my schedule is getting backed up.”
 

Why patients sign up

Retainer-based practices are still an exotic concept in many areas, but patients are beginning to understand the value, said Shalini Kaneriya, MD, an internist in Herndon, Va,, who switched her practice to concierge in 2018.

Several hundred patients followed her into her new practice because “people realized their care would be better if they had a concierge doctor,” she said. Two years ago, partly because of growing demand, she recruited another physician as an associate.

“People want a relationship with their doctor,” Dr. Serna added. “It’s hard to provide that in a regular practice.”

Todd Granger, MD, an internist who opened a DPC practice in Chapel Hill, N.C., in 2016, said new patients often mention feeling rushed through appointments with their previous doctors. Also, “it’s hard to get to see a doctor around here.”

Scott Bernstein, MD, an internist who runs a DPC practice in Scottsdale, Ariz., said he can arrange to have patients see specialists much faster than if they try to make appointments on their own. “I personally call specialists and then prep my patients on how to deal with the appointment,” he said.

Retainer-based practices tend to have a greater number of older and chronically ill patients, but they also attract patients who need less care. “The healthier patients find value in our proactive approach to prevention and wellness,” Dr. Serna said.

Some concierge physicians charge higher fees to patients who need more care, but many decide this is too complicated and charge everyone the same fee. Dr. Granger said he initially had a variable fee schedule, but when some lower-paying patients began to need more visits, he had to consider charging them extra. “Now I basically have just one fee,” he said.
 

Not a good fit for many physicians

Dr. Bauer said a lot of physicians are interested in retainer-based practice, but many of them might not make the income they had hoped for. Specialdocs interviews physicians who inquire about the model and ultimately doesn’t contract with 80% of them, Dr. Bauer said.

To be able to sign up and retain enough patients, the doctor’s attitude is important. “You have to be driven by the desire to go deep with patients -- to work hard with them and deal with their issues,” said Erika Bliss, MD, who runs a DPC practice in Seattle.

Dr. Bernstein said retainer-based physicians have to be interested in lifestyle issues, such as diet, exercise, and sleep. “I spend a lot of time dealing with issues like how to incorporate physical activity into daily routines,” he said. “Some doctors wouldn’t enjoy doing that.”

Also, concierge physicians have to be available all the time. “Patients have my cell phone number,” Dr. Granger said. “They could call in the middle of the night, but they usually don’t.”

To ensure that they get some time off, many concierge physicians have partners. Dr. Bernstein and another DPC doctor maintain separate practices but cover for each other. Each takes every other weekend off plus 6 weeks every year.
 

Can you attract enough patients?

A key challenge is finding enough patients to sustain a concierge practice. Planning the switch involves setting a target number of patients needed for the doctor to make a decent income after paying practice expenses. For example, a doctor charging $300 a month to 250 patients would gross $900,000 per year, and then pay practice expenses from that.

Attracting the target number of patients can take months or even years. After almost 6 years, Dr. Granger said, he has around 240 patients ― well below his target number of 440.

Partly because the practice model is not well known in North Carolina, Dr. Granger set his fee very low, at $60 a month, then raised it to $75. That means his practice has been grossing just $216,000 a year. But he is not about to give up. He plans to raise his fee in July and hopes that word of mouth will add more patients.

If physicians cannot earn enough in their concierge practice, Dr. Bauer said, they may moonlight at a local hospital or work for a telemedicine company. He hasn’t heard of physicians closing their concierge practice and returning to their previous practice model. “They didn’t like what they were doing before,” he said.
 

Opening up to lower-income patients

Dr. Granger’s $75 monthly fee is an example of how retainer-based medicine has transformed itself from a gold-plated service for rich people to a service that middle-class and even lower-income people can afford. DPC practices like Dr. Granger’s have dramatically lowered expenses by cutting out the need to bill insurance companies. Some DPC practices further reduce expenses by not having any staff and by renting out office space.

Dr. Forbush’s Pine Tree State patients are mostly blue-collar workers – electricians, plumbers, people who work in small businesses. He charges them $150 a month, which most patients who don’t have health insurance can afford. He said three-quarters of his patients lack health insurance, although some have back-up finances, such as health savings accounts.

Since his patients have to pay out of pocket for tests and specialists, Dr. Forbush keeps referrals in check by handling many problems himself. “Since I have more time to spend with the patient, I can often work out issues that other doctors might ask specialists to deal with,” he said.

He has learned some dermatologic procedures. “There are plenty of things I can handle on my own,” he said.

Dr. Granger adds that by examining patients during longer appointments, expensive diagnostic exams are not always necessary.
 

The challenges for this model

Many experts warn that retainer-based practices won’t work for doctors who want to leave employment or for doctors fresh out of residency. Not having your own patients to bring into the new practice is a big minus, because this is the best way to start the new practice.

Still, there are other ways to find patients. Dr. Bauer said physicians can advertise online, make themselves known by giving speeches in the community, or contract with small employers to treat their workers.

Dr. Bauer said some of his clients were employed physicians, and he thinks they will become a bigger factor now that fewer doctors remain in private practice. The chief barrier for employed physicians is the restrictive covenant that prevents them from setting up a practice nearby. But Dr. Bauer said some employers are willing to waive restrictive covenants for retainer-based doctors.

New physicians are also adopting the concierge model. Dr. Forbush said physicians straight out of residency have set up DPC practices in Maine. They signed up patients for their new practices even before they graduated, he said.

Retainer-based medicine is still mainly limited to primary care physicians, but according to Dr. Bauer, it can also work for specialists who have long-term relationships with patients, such as cardiologists, ob.gyns., rheumatologists, neurologists, and endocrinologists.
 

No going back

Most doctors who make the switch to retainer-based practice understand that there’s likely no going back. When Dr. Bernstein switched, he announced the change to patients and canceled insurance contracts. “It was make or break,” he said. “I had no parachute.”

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