Neurology

Tissue plasminogen activator (t-PA) has been the standard IV thrombolytic used in acute ischemic stroke treatment since its US Food and Drug Administration (FDA) approval in 1995. Trials have established this drug’s efficacy in the treatment of acute ischemic stroke and the appropriate patient population for therapy.^1-3 Published guidelines and experiences have made clear that a written protocol with extensive personnel training is important to deliver this care properly.⁴

Tenecteplase has been available for use in the treatment of acute myocardial infarction (MI) and studied in acute ischemic strokes since 2000. Recent large multicenter trials have suggested tenecteplase may work better than t-PA in the recanalization of large vessel occlusions (LVOs) and have provided guidance on proper dosing in acute ischemic stroke victims.^5-8 Compared with t-PA, tenecteplase has a longer half-life, is more fibrin specific (causing less coagulopathy), and is more resistant to endogenous plasminogen activator inhibitor.^9,10 Using tenecteplase for acute ischemic stroke is simpler as a single dose bolus rather than a bolus followed by a 1-hour infusion with t-PA. Immediate mechanical thrombectomy for LVO is less complicated without the 1-hour t-PA infusion.^5,6 Tenecteplase use also allows for nonthrombectomy hospitals to accelerate transfer times for patients who need thrombectomy following thrombolysis by eliminating the need for critical care nurse–staffed ambulances for interfacility transfer.¹¹ Tenecteplase also is cheaper: Tenecteplase costs $3748 per vial, whereas t-PA costs $5800 per vial equating to roughly a $2000 savings per patient.^12,13 Finally, the pharmacy formulary is simplified by using a single thrombolytic agent for both cardiac and neurologic emergencies.

Tenecteplase does have some drawbacks to consider. Currently, tenecteplase is not approved by the FDA for the indication of acute ischemic stroke, though the drug is endorsed by the American Heart Association stroke guidelines of 2019 as an alternative to t-PA.¹⁴ There is no stroke-specific preparation of the drug, leading to potential dosing errors. Therefore, a systematic process to safely transition from t-PA to tenecteplase for acute ischemic stroke was undertaken at Walter Reed National Military Medical Center (WRNMMC) in Bethesda, Maryland. Here, we report the process required in making a complex switch in thrombolytic medication along with the potential benefits of making this transition.

OBSERVATIONS

The process to implement tenecteplase required extensive training and education for staff physicians, nurses, pharmacists, radiologists, trainees, and the rapid response team. Our institution administered IV thrombolytic drugs up to 25 times annually to acute ischemic stroke victims, meaning we had to train personnel extensively and repeatedly.

In preparation for the transition to tenecteplase, hospital leadership gathered staff for multidisciplinary administrative meetings that included neurology, emergency medicine, intensive care, pharmacy, radiology, and nursing departments. The purpose of these meetings was to establish a standard operating procedure (SOP) to ensure a safe transition. This process began in May 2020 and involved regular meetings to draft and revise our SOP. Additionally, several leadership and training sessions were held over a 6-month period. Stroke boxes were developed that contained the required evaluation tools, consent forms, medications (tenecteplase and treatments for known complications), dosing cards, and instructions. Final approval of the updated acute ischemic stroke hospital policy was obtained in November 2020 and signed by the above departments.

All inclusion and exclusion criteria were determined to be the same for tenecteplase as they were for t-PA with the notable exception that the WAKE-UP trial protocol would not be supported until further evidence became available.⁹ The results of the WAKE-UP trial had previously been used at WRNMMC to justify administration of t-PA in patients who awoke with symptoms of acute ischemic stroke, the last known well was unclear or > 4.5 hours, and for whom a magnetic resonance imaging (MRI) of the brain could be obtained rapidly. Based on the WAKE-UP trial, if the MRI scan of the brain in these patients demonstrated restricted diffusion without fluid attenuated inversion recovery (FLAIR) signal changes (diffusion-weighted [DWI]-FLAIR mismatch sign), this indicated that the stroke had likely occurred recently, and it was safe to administer t-PA. This allowed for administration of t-PA outside the standard treatment window of 4.5 hours from last known well, especially in the cases of patients who awoke with symptoms.

Since safety data are not yet available for the use of tenecteplase in this fashion, the WAKE-UP trial protocol was not used as an inclusion criterion. The informed consent form was modified, and the following scenarios were outlined: (1) If the patient or surrogate is immediately available to consent, paper consent will be documented with the additional note that tenecteplase is being used off-label; and (2) If the patient cannot consent and a surrogate is not immediately available, the medicine will be used emergently as long as the neurology resident and attending physicians agree.¹⁵

Risk mitigation was considered carefully. The stroke box described above is stocked and maintained by the pharmacy as we have transitioned to using designated pharmacists for the storage and preparation of tenecteplase. We highly recommend the use of designated pharmacists or emergency department pharmacists in this manner to avoid dosing errors.^7,16 Since the current pharmacy-provided tenecteplase bottle contains twice the maximum dose indicated for ischemic stroke, only a 5 mL syringe is included in the stroke box to ensure a maximum dose of 25 mg is drawn up after reconstitution. Dosing card charts were made like existing dosing card charts for t-PA to quickly calculate the 0.25 mg/kg dose. In training, the difference in dosing in ischemic stroke was emphasized. Finally, pharmacy has taken responsibility for dosing the medication during stroke codes.

Any medical personnel at WRNMMC can initiate a stroke code by sending a page to the neurology consult service (Figure).

TRANSITION AND RESULTS

From November 2020 to December 2021, 10 patients have been treated in total at WRNMMC (Table).

CONCLUSIONS

The available evidence supports the transition from t-PA to tenecteplase for acute ischemic stroke. The successful transition required months of preparation involving multidisciplinary meetings between neurology, nursing, pharmacy, radiology, rapid response teams, critical care, and emergency medicine departments. Safeguards must be implemented to avoid a tenecteplase dosing error that can lead to potentially life-threatening adverse effects. The results at WRNMMC thus far are promising for safety and efficacy. Several process improvements are planned: a hospital-wide overhead page will accompany the direct page to neurology; other team members, including radiology and pharmacy, will be included on the acute stroke alert; and a stroke-specific paging application will be implemented to better track real-time stroke metrics and improve flow. These measures mirror processes that are occurring in institutions that treat acute stroke patients.

Tissue plasminogen activator (t-PA) has been the standard IV thrombolytic used in acute ischemic stroke treatment since its US Food and Drug Administration (FDA) approval in 1995. Trials have established this drug’s efficacy in the treatment of acute ischemic stroke and the appropriate patient population for therapy.^1-3 Published guidelines and experiences have made clear that a written protocol with extensive personnel training is important to deliver this care properly.⁴

Tenecteplase has been available for use in the treatment of acute myocardial infarction (MI) and studied in acute ischemic strokes since 2000. Recent large multicenter trials have suggested tenecteplase may work better than t-PA in the recanalization of large vessel occlusions (LVOs) and have provided guidance on proper dosing in acute ischemic stroke victims.^5-8 Compared with t-PA, tenecteplase has a longer half-life, is more fibrin specific (causing less coagulopathy), and is more resistant to endogenous plasminogen activator inhibitor.^9,10 Using tenecteplase for acute ischemic stroke is simpler as a single dose bolus rather than a bolus followed by a 1-hour infusion with t-PA. Immediate mechanical thrombectomy for LVO is less complicated without the 1-hour t-PA infusion.^5,6 Tenecteplase use also allows for nonthrombectomy hospitals to accelerate transfer times for patients who need thrombectomy following thrombolysis by eliminating the need for critical care nurse–staffed ambulances for interfacility transfer.¹¹ Tenecteplase also is cheaper: Tenecteplase costs $3748 per vial, whereas t-PA costs $5800 per vial equating to roughly a $2000 savings per patient.^12,13 Finally, the pharmacy formulary is simplified by using a single thrombolytic agent for both cardiac and neurologic emergencies.

Tenecteplase does have some drawbacks to consider. Currently, tenecteplase is not approved by the FDA for the indication of acute ischemic stroke, though the drug is endorsed by the American Heart Association stroke guidelines of 2019 as an alternative to t-PA.¹⁴ There is no stroke-specific preparation of the drug, leading to potential dosing errors. Therefore, a systematic process to safely transition from t-PA to tenecteplase for acute ischemic stroke was undertaken at Walter Reed National Military Medical Center (WRNMMC) in Bethesda, Maryland. Here, we report the process required in making a complex switch in thrombolytic medication along with the potential benefits of making this transition.

OBSERVATIONS

The process to implement tenecteplase required extensive training and education for staff physicians, nurses, pharmacists, radiologists, trainees, and the rapid response team. Our institution administered IV thrombolytic drugs up to 25 times annually to acute ischemic stroke victims, meaning we had to train personnel extensively and repeatedly.

In preparation for the transition to tenecteplase, hospital leadership gathered staff for multidisciplinary administrative meetings that included neurology, emergency medicine, intensive care, pharmacy, radiology, and nursing departments. The purpose of these meetings was to establish a standard operating procedure (SOP) to ensure a safe transition. This process began in May 2020 and involved regular meetings to draft and revise our SOP. Additionally, several leadership and training sessions were held over a 6-month period. Stroke boxes were developed that contained the required evaluation tools, consent forms, medications (tenecteplase and treatments for known complications), dosing cards, and instructions. Final approval of the updated acute ischemic stroke hospital policy was obtained in November 2020 and signed by the above departments.

All inclusion and exclusion criteria were determined to be the same for tenecteplase as they were for t-PA with the notable exception that the WAKE-UP trial protocol would not be supported until further evidence became available.⁹ The results of the WAKE-UP trial had previously been used at WRNMMC to justify administration of t-PA in patients who awoke with symptoms of acute ischemic stroke, the last known well was unclear or > 4.5 hours, and for whom a magnetic resonance imaging (MRI) of the brain could be obtained rapidly. Based on the WAKE-UP trial, if the MRI scan of the brain in these patients demonstrated restricted diffusion without fluid attenuated inversion recovery (FLAIR) signal changes (diffusion-weighted [DWI]-FLAIR mismatch sign), this indicated that the stroke had likely occurred recently, and it was safe to administer t-PA. This allowed for administration of t-PA outside the standard treatment window of 4.5 hours from last known well, especially in the cases of patients who awoke with symptoms.

Since safety data are not yet available for the use of tenecteplase in this fashion, the WAKE-UP trial protocol was not used as an inclusion criterion. The informed consent form was modified, and the following scenarios were outlined: (1) If the patient or surrogate is immediately available to consent, paper consent will be documented with the additional note that tenecteplase is being used off-label; and (2) If the patient cannot consent and a surrogate is not immediately available, the medicine will be used emergently as long as the neurology resident and attending physicians agree.¹⁵

Risk mitigation was considered carefully. The stroke box described above is stocked and maintained by the pharmacy as we have transitioned to using designated pharmacists for the storage and preparation of tenecteplase. We highly recommend the use of designated pharmacists or emergency department pharmacists in this manner to avoid dosing errors.^7,16 Since the current pharmacy-provided tenecteplase bottle contains twice the maximum dose indicated for ischemic stroke, only a 5 mL syringe is included in the stroke box to ensure a maximum dose of 25 mg is drawn up after reconstitution. Dosing card charts were made like existing dosing card charts for t-PA to quickly calculate the 0.25 mg/kg dose. In training, the difference in dosing in ischemic stroke was emphasized. Finally, pharmacy has taken responsibility for dosing the medication during stroke codes.

Any medical personnel at WRNMMC can initiate a stroke code by sending a page to the neurology consult service (Figure).

TRANSITION AND RESULTS

From November 2020 to December 2021, 10 patients have been treated in total at WRNMMC (Table).

CONCLUSIONS

The available evidence supports the transition from t-PA to tenecteplase for acute ischemic stroke. The successful transition required months of preparation involving multidisciplinary meetings between neurology, nursing, pharmacy, radiology, rapid response teams, critical care, and emergency medicine departments. Safeguards must be implemented to avoid a tenecteplase dosing error that can lead to potentially life-threatening adverse effects. The results at WRNMMC thus far are promising for safety and efficacy. Several process improvements are planned: a hospital-wide overhead page will accompany the direct page to neurology; other team members, including radiology and pharmacy, will be included on the acute stroke alert; and a stroke-specific paging application will be implemented to better track real-time stroke metrics and improve flow. These measures mirror processes that are occurring in institutions that treat acute stroke patients.

Tissue plasminogen activator (t-PA) has been the standard IV thrombolytic used in acute ischemic stroke treatment since its US Food and Drug Administration (FDA) approval in 1995. Trials have established this drug’s efficacy in the treatment of acute ischemic stroke and the appropriate patient population for therapy.^1-3 Published guidelines and experiences have made clear that a written protocol with extensive personnel training is important to deliver this care properly.⁴

Tenecteplase has been available for use in the treatment of acute myocardial infarction (MI) and studied in acute ischemic strokes since 2000. Recent large multicenter trials have suggested tenecteplase may work better than t-PA in the recanalization of large vessel occlusions (LVOs) and have provided guidance on proper dosing in acute ischemic stroke victims.^5-8 Compared with t-PA, tenecteplase has a longer half-life, is more fibrin specific (causing less coagulopathy), and is more resistant to endogenous plasminogen activator inhibitor.^9,10 Using tenecteplase for acute ischemic stroke is simpler as a single dose bolus rather than a bolus followed by a 1-hour infusion with t-PA. Immediate mechanical thrombectomy for LVO is less complicated without the 1-hour t-PA infusion.^5,6 Tenecteplase use also allows for nonthrombectomy hospitals to accelerate transfer times for patients who need thrombectomy following thrombolysis by eliminating the need for critical care nurse–staffed ambulances for interfacility transfer.¹¹ Tenecteplase also is cheaper: Tenecteplase costs $3748 per vial, whereas t-PA costs $5800 per vial equating to roughly a $2000 savings per patient.^12,13 Finally, the pharmacy formulary is simplified by using a single thrombolytic agent for both cardiac and neurologic emergencies.

Tenecteplase does have some drawbacks to consider. Currently, tenecteplase is not approved by the FDA for the indication of acute ischemic stroke, though the drug is endorsed by the American Heart Association stroke guidelines of 2019 as an alternative to t-PA.¹⁴ There is no stroke-specific preparation of the drug, leading to potential dosing errors. Therefore, a systematic process to safely transition from t-PA to tenecteplase for acute ischemic stroke was undertaken at Walter Reed National Military Medical Center (WRNMMC) in Bethesda, Maryland. Here, we report the process required in making a complex switch in thrombolytic medication along with the potential benefits of making this transition.

OBSERVATIONS

The process to implement tenecteplase required extensive training and education for staff physicians, nurses, pharmacists, radiologists, trainees, and the rapid response team. Our institution administered IV thrombolytic drugs up to 25 times annually to acute ischemic stroke victims, meaning we had to train personnel extensively and repeatedly.

In preparation for the transition to tenecteplase, hospital leadership gathered staff for multidisciplinary administrative meetings that included neurology, emergency medicine, intensive care, pharmacy, radiology, and nursing departments. The purpose of these meetings was to establish a standard operating procedure (SOP) to ensure a safe transition. This process began in May 2020 and involved regular meetings to draft and revise our SOP. Additionally, several leadership and training sessions were held over a 6-month period. Stroke boxes were developed that contained the required evaluation tools, consent forms, medications (tenecteplase and treatments for known complications), dosing cards, and instructions. Final approval of the updated acute ischemic stroke hospital policy was obtained in November 2020 and signed by the above departments.

All inclusion and exclusion criteria were determined to be the same for tenecteplase as they were for t-PA with the notable exception that the WAKE-UP trial protocol would not be supported until further evidence became available.⁹ The results of the WAKE-UP trial had previously been used at WRNMMC to justify administration of t-PA in patients who awoke with symptoms of acute ischemic stroke, the last known well was unclear or > 4.5 hours, and for whom a magnetic resonance imaging (MRI) of the brain could be obtained rapidly. Based on the WAKE-UP trial, if the MRI scan of the brain in these patients demonstrated restricted diffusion without fluid attenuated inversion recovery (FLAIR) signal changes (diffusion-weighted [DWI]-FLAIR mismatch sign), this indicated that the stroke had likely occurred recently, and it was safe to administer t-PA. This allowed for administration of t-PA outside the standard treatment window of 4.5 hours from last known well, especially in the cases of patients who awoke with symptoms.

Since safety data are not yet available for the use of tenecteplase in this fashion, the WAKE-UP trial protocol was not used as an inclusion criterion. The informed consent form was modified, and the following scenarios were outlined: (1) If the patient or surrogate is immediately available to consent, paper consent will be documented with the additional note that tenecteplase is being used off-label; and (2) If the patient cannot consent and a surrogate is not immediately available, the medicine will be used emergently as long as the neurology resident and attending physicians agree.¹⁵

Risk mitigation was considered carefully. The stroke box described above is stocked and maintained by the pharmacy as we have transitioned to using designated pharmacists for the storage and preparation of tenecteplase. We highly recommend the use of designated pharmacists or emergency department pharmacists in this manner to avoid dosing errors.^7,16 Since the current pharmacy-provided tenecteplase bottle contains twice the maximum dose indicated for ischemic stroke, only a 5 mL syringe is included in the stroke box to ensure a maximum dose of 25 mg is drawn up after reconstitution. Dosing card charts were made like existing dosing card charts for t-PA to quickly calculate the 0.25 mg/kg dose. In training, the difference in dosing in ischemic stroke was emphasized. Finally, pharmacy has taken responsibility for dosing the medication during stroke codes.

Any medical personnel at WRNMMC can initiate a stroke code by sending a page to the neurology consult service (Figure).

TRANSITION AND RESULTS

From November 2020 to December 2021, 10 patients have been treated in total at WRNMMC (Table).

CONCLUSIONS

The available evidence supports the transition from t-PA to tenecteplase for acute ischemic stroke. The successful transition required months of preparation involving multidisciplinary meetings between neurology, nursing, pharmacy, radiology, rapid response teams, critical care, and emergency medicine departments. Safeguards must be implemented to avoid a tenecteplase dosing error that can lead to potentially life-threatening adverse effects. The results at WRNMMC thus far are promising for safety and efficacy. Several process improvements are planned: a hospital-wide overhead page will accompany the direct page to neurology; other team members, including radiology and pharmacy, will be included on the acute stroke alert; and a stroke-specific paging application will be implemented to better track real-time stroke metrics and improve flow. These measures mirror processes that are occurring in institutions that treat acute stroke patients.

Long COVID is typically characterized by anosmia and dysgeusia, cognitive impairment, dyspnea, weakness, and palpitations, with younger patients showing greatest improvements at 1 year, according to a nationwide cohort study conducted in Israel.

These findings help define long COVID, guiding providers and patients through the recovery process, Barak Mizrahi, MSc, of KI Research Institute, Kfar Malal, Israel, and colleagues reported.

“To provide efficient continuous treatment and prevent adverse events related to potential long term effects and delayed symptoms of COVID-19, determining the magnitude and severity of this phenomenon and distinguishing it from similar clinical manifestations that occur normally or following infections with other pathogens is essential,” the investigators wrote in The BMJ.

To this end, they conducted a retrospective, nationwide cohort study involving 1,913,234 people who took a polymerase chain reaction test for SARS-CoV-2 between March 1, 2020, and Oct. 1, 2021. They compared a range of long-term outcomes at different intervals post infection, and compared these trends across subgroups sorted by age, sex, and variant. Outcomes ranged broadly, including respiratory disorders, cough, arthralgia, weakness, hair loss, and others.

The investigators compared hazard ratios for each of these outcomes among patients who tested positive versus those who tested negative at three intervals after testing: 30-90 days, 30-180 days, and 180-360 days. Statistically significant differences in the risks of these outcomes between infected versus uninfected groups suggested that COVID was playing a role.

“The health outcomes that represent long COVID showed a significant increase in both early and late phases,” the investigators wrote. These outcomes included anosmia and dysgeusia, cognitive impairment, dyspnea, weakness, and palpitations. In contrast, chest pain, myalgia, arthralgia, cough, and dizziness were associated with patients who were in the early phase, but not the late phase of long COVID.

“Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnea and similar risk for other outcomes compared with unvaccinated infected patients,” the investigators noted.

For the long COVID outcomes, plots of risk differences over time showed that symptoms tended to get milder or resolve within a few months to a year. Patients 41-60 years were most likely to be impacted by long COVID outcomes, and show least improvement at 1 year, compared with other age groups.

“We believe that these findings will shed light on what is ‘long COVID’, support patients and doctors, and facilitate better and more efficient care,” Mr. Mizrahi and coauthor Maytal Bivas-Benita, PhD said in a joint written comment. “Primary care physicians (and patients) will now more clearly understand what are the symptoms that might be related to COVID and for how long they might linger. This would help physicians monitor the patients efficiently, ease their patients’ concerns and navigate a more efficient disease management.”

They suggested that the findings should hold consistent for future variants, although they could not “rule out the possibility of the emergence of new and more severe variants which will be more virulent and cause a more severe illness.”

One “major limitation” of the study, according to Monica Verduzco-Gutierrez, MD, a physiatrist and professor and chair of rehabilitation medicine at the University of Texas Health Science Center, San Antonio, is the lack of data for fatigue and dysautonomia, which are “the major presentations” that she sees in her long COVID clinic.

“The authors of the article focus on the primary damage being related to the lungs, though we know this is a systemic disease beyond the respiratory system, with endothelial dysfunction and immune dysregulation,” Dr. Verduzco-Gutierrez, who is also director of COVID recovery at the University of Texas Health Science Center, said in an interview.

Although it was reassuring to see that younger adults with long COVID trended toward improvement, she noted that patients 41-60 years “still had pretty significant symptoms” after 12 months.

“That [age group comprises] probably the majority of my patients that I’m seeing in the long COVID clinic,” Dr. Verduzco-Gutierrez said. “If you look at the whole thing, it looks better, but then when you drill down to that age group where you’re seeing patients, then it’s not.”

Dr. Verduzco-Gutierrez is so busy managing patients with long COVID that new appointments in her clinic are now delayed until May 31, so most patients will remain under the care of their primary care providers. She recommended that these physicians follow guidance from the American Academy of Physical Medicine and Rehabilitation, who offer consensus statements based on clinical characteristics, with separate recommendations for pediatric patients.

Our understanding of long COVID will continue to improve, and with it, available recommendations, she predicted, but further advances will require persistent effort.

“I think no matter what this [study] shows us, more research is needed,” Dr. Verduzco-Gutierrez said. “We can’t just forget about it, just because there is a population of people who get better. What about the ones who don’t?”

The investigators and Dr. Verduzco-Gutierrez disclosed no conflicts of interest.

Long COVID is typically characterized by anosmia and dysgeusia, cognitive impairment, dyspnea, weakness, and palpitations, with younger patients showing greatest improvements at 1 year, according to a nationwide cohort study conducted in Israel.

These findings help define long COVID, guiding providers and patients through the recovery process, Barak Mizrahi, MSc, of KI Research Institute, Kfar Malal, Israel, and colleagues reported.

“To provide efficient continuous treatment and prevent adverse events related to potential long term effects and delayed symptoms of COVID-19, determining the magnitude and severity of this phenomenon and distinguishing it from similar clinical manifestations that occur normally or following infections with other pathogens is essential,” the investigators wrote in The BMJ.

To this end, they conducted a retrospective, nationwide cohort study involving 1,913,234 people who took a polymerase chain reaction test for SARS-CoV-2 between March 1, 2020, and Oct. 1, 2021. They compared a range of long-term outcomes at different intervals post infection, and compared these trends across subgroups sorted by age, sex, and variant. Outcomes ranged broadly, including respiratory disorders, cough, arthralgia, weakness, hair loss, and others.

The investigators compared hazard ratios for each of these outcomes among patients who tested positive versus those who tested negative at three intervals after testing: 30-90 days, 30-180 days, and 180-360 days. Statistically significant differences in the risks of these outcomes between infected versus uninfected groups suggested that COVID was playing a role.

“The health outcomes that represent long COVID showed a significant increase in both early and late phases,” the investigators wrote. These outcomes included anosmia and dysgeusia, cognitive impairment, dyspnea, weakness, and palpitations. In contrast, chest pain, myalgia, arthralgia, cough, and dizziness were associated with patients who were in the early phase, but not the late phase of long COVID.

“Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnea and similar risk for other outcomes compared with unvaccinated infected patients,” the investigators noted.

For the long COVID outcomes, plots of risk differences over time showed that symptoms tended to get milder or resolve within a few months to a year. Patients 41-60 years were most likely to be impacted by long COVID outcomes, and show least improvement at 1 year, compared with other age groups.

“We believe that these findings will shed light on what is ‘long COVID’, support patients and doctors, and facilitate better and more efficient care,” Mr. Mizrahi and coauthor Maytal Bivas-Benita, PhD said in a joint written comment. “Primary care physicians (and patients) will now more clearly understand what are the symptoms that might be related to COVID and for how long they might linger. This would help physicians monitor the patients efficiently, ease their patients’ concerns and navigate a more efficient disease management.”

They suggested that the findings should hold consistent for future variants, although they could not “rule out the possibility of the emergence of new and more severe variants which will be more virulent and cause a more severe illness.”

One “major limitation” of the study, according to Monica Verduzco-Gutierrez, MD, a physiatrist and professor and chair of rehabilitation medicine at the University of Texas Health Science Center, San Antonio, is the lack of data for fatigue and dysautonomia, which are “the major presentations” that she sees in her long COVID clinic.

“The authors of the article focus on the primary damage being related to the lungs, though we know this is a systemic disease beyond the respiratory system, with endothelial dysfunction and immune dysregulation,” Dr. Verduzco-Gutierrez, who is also director of COVID recovery at the University of Texas Health Science Center, said in an interview.

Although it was reassuring to see that younger adults with long COVID trended toward improvement, she noted that patients 41-60 years “still had pretty significant symptoms” after 12 months.

“That [age group comprises] probably the majority of my patients that I’m seeing in the long COVID clinic,” Dr. Verduzco-Gutierrez said. “If you look at the whole thing, it looks better, but then when you drill down to that age group where you’re seeing patients, then it’s not.”

Dr. Verduzco-Gutierrez is so busy managing patients with long COVID that new appointments in her clinic are now delayed until May 31, so most patients will remain under the care of their primary care providers. She recommended that these physicians follow guidance from the American Academy of Physical Medicine and Rehabilitation, who offer consensus statements based on clinical characteristics, with separate recommendations for pediatric patients.

Our understanding of long COVID will continue to improve, and with it, available recommendations, she predicted, but further advances will require persistent effort.

“I think no matter what this [study] shows us, more research is needed,” Dr. Verduzco-Gutierrez said. “We can’t just forget about it, just because there is a population of people who get better. What about the ones who don’t?”

The investigators and Dr. Verduzco-Gutierrez disclosed no conflicts of interest.

Long COVID is typically characterized by anosmia and dysgeusia, cognitive impairment, dyspnea, weakness, and palpitations, with younger patients showing greatest improvements at 1 year, according to a nationwide cohort study conducted in Israel.

These findings help define long COVID, guiding providers and patients through the recovery process, Barak Mizrahi, MSc, of KI Research Institute, Kfar Malal, Israel, and colleagues reported.

“To provide efficient continuous treatment and prevent adverse events related to potential long term effects and delayed symptoms of COVID-19, determining the magnitude and severity of this phenomenon and distinguishing it from similar clinical manifestations that occur normally or following infections with other pathogens is essential,” the investigators wrote in The BMJ.

To this end, they conducted a retrospective, nationwide cohort study involving 1,913,234 people who took a polymerase chain reaction test for SARS-CoV-2 between March 1, 2020, and Oct. 1, 2021. They compared a range of long-term outcomes at different intervals post infection, and compared these trends across subgroups sorted by age, sex, and variant. Outcomes ranged broadly, including respiratory disorders, cough, arthralgia, weakness, hair loss, and others.

The investigators compared hazard ratios for each of these outcomes among patients who tested positive versus those who tested negative at three intervals after testing: 30-90 days, 30-180 days, and 180-360 days. Statistically significant differences in the risks of these outcomes between infected versus uninfected groups suggested that COVID was playing a role.

“The health outcomes that represent long COVID showed a significant increase in both early and late phases,” the investigators wrote. These outcomes included anosmia and dysgeusia, cognitive impairment, dyspnea, weakness, and palpitations. In contrast, chest pain, myalgia, arthralgia, cough, and dizziness were associated with patients who were in the early phase, but not the late phase of long COVID.

“Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnea and similar risk for other outcomes compared with unvaccinated infected patients,” the investigators noted.

For the long COVID outcomes, plots of risk differences over time showed that symptoms tended to get milder or resolve within a few months to a year. Patients 41-60 years were most likely to be impacted by long COVID outcomes, and show least improvement at 1 year, compared with other age groups.

“We believe that these findings will shed light on what is ‘long COVID’, support patients and doctors, and facilitate better and more efficient care,” Mr. Mizrahi and coauthor Maytal Bivas-Benita, PhD said in a joint written comment. “Primary care physicians (and patients) will now more clearly understand what are the symptoms that might be related to COVID and for how long they might linger. This would help physicians monitor the patients efficiently, ease their patients’ concerns and navigate a more efficient disease management.”

They suggested that the findings should hold consistent for future variants, although they could not “rule out the possibility of the emergence of new and more severe variants which will be more virulent and cause a more severe illness.”

One “major limitation” of the study, according to Monica Verduzco-Gutierrez, MD, a physiatrist and professor and chair of rehabilitation medicine at the University of Texas Health Science Center, San Antonio, is the lack of data for fatigue and dysautonomia, which are “the major presentations” that she sees in her long COVID clinic.

“The authors of the article focus on the primary damage being related to the lungs, though we know this is a systemic disease beyond the respiratory system, with endothelial dysfunction and immune dysregulation,” Dr. Verduzco-Gutierrez, who is also director of COVID recovery at the University of Texas Health Science Center, said in an interview.

Although it was reassuring to see that younger adults with long COVID trended toward improvement, she noted that patients 41-60 years “still had pretty significant symptoms” after 12 months.

“That [age group comprises] probably the majority of my patients that I’m seeing in the long COVID clinic,” Dr. Verduzco-Gutierrez said. “If you look at the whole thing, it looks better, but then when you drill down to that age group where you’re seeing patients, then it’s not.”

Dr. Verduzco-Gutierrez is so busy managing patients with long COVID that new appointments in her clinic are now delayed until May 31, so most patients will remain under the care of their primary care providers. She recommended that these physicians follow guidance from the American Academy of Physical Medicine and Rehabilitation, who offer consensus statements based on clinical characteristics, with separate recommendations for pediatric patients.

Our understanding of long COVID will continue to improve, and with it, available recommendations, she predicted, but further advances will require persistent effort.

“I think no matter what this [study] shows us, more research is needed,” Dr. Verduzco-Gutierrez said. “We can’t just forget about it, just because there is a population of people who get better. What about the ones who don’t?”

The investigators and Dr. Verduzco-Gutierrez disclosed no conflicts of interest.

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

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

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

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

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show.

Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore, Md., told this news organization.

The findings were published online in JAMA.
 

Dose-dependent effect

For the study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study were collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than those with normal hearing (prevalence ratio, 1.61; 95% confidence interval, 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate/severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assistive devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). This news organization last month reported on similar data published in JAMA Neurology suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show.

Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore, Md., told this news organization.

The findings were published online in JAMA.
 

Dose-dependent effect

For the study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study were collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than those with normal hearing (prevalence ratio, 1.61; 95% confidence interval, 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate/severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assistive devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). This news organization last month reported on similar data published in JAMA Neurology suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show.

Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore, Md., told this news organization.

The findings were published online in JAMA.
 

Dose-dependent effect

For the study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study were collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than those with normal hearing (prevalence ratio, 1.61; 95% confidence interval, 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate/severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assistive devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). This news organization last month reported on similar data published in JAMA Neurology suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships.

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

Telehealth parent-child interaction therapy improved the behavior of 3-year-olds with developmental delay in a randomized controlled trial.

The children received the therapy with their parents or caregivers, who were more likely to demonstrate positive parenting behaviors than parents in the control group, authors of the new research published in JAMA Pediatrics found.

Approximately 13% of children have some form of developmental delay (DD) and more than half of these children also have at least one mental health disorder, which makes behavior problems a common and ongoing challenge, Daniel M. Bagner, PhD, a psychologist at Florida International University, Miami, and colleagues wrote.

Clinic-based interventions such as parent-child interaction therapy (PCIT) have been effective for improving behavior in children with DD, the researchers said. PCIT involves in-session caregiver coaching using a 1-way mirror and a wireless earpiece worn by the caregiver.

Barriers to the use of PCIT, especially in marginalized and low-income communities, include transportation, clinician shortages, and stigma-related concerns about a clinic visit, the researchers wrote. Technology now allows for Internet-delivered PCIT to reach more children and families, but its effectiveness for children with DD has not been well studied.

In the new study, the researchers randomized 150 children with DD and externalizing behavior problems to up to 20 weeks of Internet-delivered parent-child interaction therapy (iPCIT) or to referral as usual (RAU, the control group). The children were randomized after completion of early intervention services within 3 months of their third birthday, and participated in the sessions with a parent or caregiver. Most of the participants were from economically disadvantaged households and underrepresented ethnic backgrounds.

The iPCIT intervention was conducted weekly with a remote therapist and lasted for 1-1.5 hours; approximately half of the families received the intervention in Spanish.

The primary outcome was rating on the Child Behavior Checklist (CBCL) and assessment of children and caregivers using the Dyadic Parent-Child Interaction Coding System, fourth edition (DPICS). Assessments occurred at baseline and at week 20 (post treatment), with follow ups at 6 and 12 months.

Scores on the CBCL in the iPCIT group decreased from a mean of 61.18 at baseline to 53.83 post intervention. Scores for the control group started at 64.05 and decreased to 59.49 post intervention. At 6-12 months, the scores for both groups remained stable.

Children who received iPCIT with their parent or caregiver also showed significantly lower levels of externalizing behavior problems, compared with the RAU controls post treatment, and at 6-month and 12-month follow-ups based on the Cohen d measure of standardized effect size for differences between groups.

Significantly more children in the iPCIT group showed clinically significant improvements in externalizing problems at post treatment, compared with the RAU group (74% vs. 42%; P < .001) and at 6 months’ follow-up (73% vs. 45%; P = .002). However, the differences from baseline were not significantly different between the two groups after 12 months, which suggests that the effects may wane over time, the researchers noted.

In addition, the rate of child compliance with parent commands, as measured by a cleanup task, approximately doubled by the 12-month follow-up among children in the iPCIT group versus an increase of approximately one-third in the RAU group.

For secondary outcome measures related to caregiver behaviors, the proportion of observed positive parenting behaviors increased in the iPCIT group during the course of the intervention (postintervention odds ratio, 1.10), and the proportion of controlling and critical behaviors decreased (postintervention OR, 1.40). Harsh and inconsistent discipline decreased in both groups based on self-reports, but the decrease was steeper in iPCIT families.

iPCIT did not have a greater impact than RAU in reducing caregiver stress. The researchers wrote that they were not surprised by the lack of stress reduction “given mixed findings on the impact of parenting interventions on stress in caregivers of children with DD.”
 

Data support iPCIT potential

Overall, the results support findings from previous studies of clinic-based PCIT for children with DD and previous studies of telehealth interventions for typically developing children, the researchers said.

“Moreover, iPCIT-treated children not only showed reductions in behavior problems, such as aggression, but demonstrated higher rates of following directions, which is especially important for children entering kindergarten,” they wrote.

The findings were limited by several factors including the narrow focus on the primary and secondary outcomes, the use of data from a single site in a single metropolitan area – which may limit generalizability – and the lack of comparison between iPCIT and a clinic-based PCIT control group, the researchers noted. The equipment in the current study was provided to families; therefore, differences in treatment response could not be attributed to differences in technology.

The study represents the first known randomized controlled trial to evaluate a telehealth parenting intervention for children with, according to the researchers. The results suggest that technology can be leveraged to help these patients, including those from ethnic minority families who may be underserved by clinic-based care in overcoming barriers to treatment such as transportation and availability of clinicians. Use of iPCIT could be a critical resource as young children with DD complete Part C services and enter the school system.
 

Practical pediatric takeaways

“This was a great study, well-designed and very important and helpful for pediatric providers,” Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Young children with developmental delay and/or mental and behavioral health disorders require early identification and intervention,” said Dr. Haut. However, obstacles to intervention include stigma or parental denial of the disorder, as well as more practical challenges related to transportation, time to access a clinic or office, potential long length of treatment, and cost.

“Despite availability of state programs for young children, follow up and continued services can be challenging to complete. Once the child outgrows the state program finding alternative therapy can be difficult with the current shortage of pediatric mental health providers,” Dr. Haut noted.

“I was surprised to see that this study treatment phase was completed prior to the COVID-19 pandemic, when telehealth was not as popular a mode for health care and was not utilized to the extent that it is now, especially for pediatric care,” said Dr. Haut. “I was not surprised at the results, as the traditional mode of PCIT includes therapy and training in a space that may not be as familiar to the child as their home environment, and would include live presence of the therapist/s, which may add to anxiety for both the parent and child.”

That almost half of the parents participating in the study had graduated from college and/or completed graduate degrees “may have contributed to some of the success of this study,” Dr. Haut noted.
 

Benefits and barriers

“The COVID-19 pandemic brought significant change to the frequency of use and overall success of telehealth services,” Dr. Haut said. “Additional provider education in aspects such as provider technique and the use of medical devices with improved specific health care technology assisted in advancing the experience and opportunity for successful telehealth visits. Telehealth therapy offers a cost-effective option for any pediatric patients and for providers, as the time and space commitment for the patient visit can be considerably less than live office visits.

“Unfortunately, there are still overall barriers that I have personally experienced with telehealth, including interruptions in connectivity, background noise, and lack of an available computer or tablet; and with the use of cell phones not always allowing full inclusion of the caregiver and child,” said Dr. Haut. Children with DD, behavioral problems, or other mental health disorders may pose challenges for parents to manage at home while simultaneously trying to fully focus on the therapy in an online setting.

Although the current study is encouraging, “larger studies focused on specific or individual pediatric mental health and/or behavioral disorders may offer more information for providers, and better document the success of telehealth delivery of services,” Dr. Haut said.

The study was supported by the National Institute of Child Health and Human Development. Dr. Bagner disclosed funding from the National Institutes of Health. He also disclosed personal fees from PCIT International to train clinicians in PCIT supported by a grant from the Florida Department of Children and Families outside the current study. Dr. Haut had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.

Telehealth parent-child interaction therapy improved the behavior of 3-year-olds with developmental delay in a randomized controlled trial.

The children received the therapy with their parents or caregivers, who were more likely to demonstrate positive parenting behaviors than parents in the control group, authors of the new research published in JAMA Pediatrics found.

Approximately 13% of children have some form of developmental delay (DD) and more than half of these children also have at least one mental health disorder, which makes behavior problems a common and ongoing challenge, Daniel M. Bagner, PhD, a psychologist at Florida International University, Miami, and colleagues wrote.

Clinic-based interventions such as parent-child interaction therapy (PCIT) have been effective for improving behavior in children with DD, the researchers said. PCIT involves in-session caregiver coaching using a 1-way mirror and a wireless earpiece worn by the caregiver.

Barriers to the use of PCIT, especially in marginalized and low-income communities, include transportation, clinician shortages, and stigma-related concerns about a clinic visit, the researchers wrote. Technology now allows for Internet-delivered PCIT to reach more children and families, but its effectiveness for children with DD has not been well studied.

In the new study, the researchers randomized 150 children with DD and externalizing behavior problems to up to 20 weeks of Internet-delivered parent-child interaction therapy (iPCIT) or to referral as usual (RAU, the control group). The children were randomized after completion of early intervention services within 3 months of their third birthday, and participated in the sessions with a parent or caregiver. Most of the participants were from economically disadvantaged households and underrepresented ethnic backgrounds.

The iPCIT intervention was conducted weekly with a remote therapist and lasted for 1-1.5 hours; approximately half of the families received the intervention in Spanish.

The primary outcome was rating on the Child Behavior Checklist (CBCL) and assessment of children and caregivers using the Dyadic Parent-Child Interaction Coding System, fourth edition (DPICS). Assessments occurred at baseline and at week 20 (post treatment), with follow ups at 6 and 12 months.

Scores on the CBCL in the iPCIT group decreased from a mean of 61.18 at baseline to 53.83 post intervention. Scores for the control group started at 64.05 and decreased to 59.49 post intervention. At 6-12 months, the scores for both groups remained stable.

Children who received iPCIT with their parent or caregiver also showed significantly lower levels of externalizing behavior problems, compared with the RAU controls post treatment, and at 6-month and 12-month follow-ups based on the Cohen d measure of standardized effect size for differences between groups.

Significantly more children in the iPCIT group showed clinically significant improvements in externalizing problems at post treatment, compared with the RAU group (74% vs. 42%; P < .001) and at 6 months’ follow-up (73% vs. 45%; P = .002). However, the differences from baseline were not significantly different between the two groups after 12 months, which suggests that the effects may wane over time, the researchers noted.

In addition, the rate of child compliance with parent commands, as measured by a cleanup task, approximately doubled by the 12-month follow-up among children in the iPCIT group versus an increase of approximately one-third in the RAU group.

For secondary outcome measures related to caregiver behaviors, the proportion of observed positive parenting behaviors increased in the iPCIT group during the course of the intervention (postintervention odds ratio, 1.10), and the proportion of controlling and critical behaviors decreased (postintervention OR, 1.40). Harsh and inconsistent discipline decreased in both groups based on self-reports, but the decrease was steeper in iPCIT families.

iPCIT did not have a greater impact than RAU in reducing caregiver stress. The researchers wrote that they were not surprised by the lack of stress reduction “given mixed findings on the impact of parenting interventions on stress in caregivers of children with DD.”
 

Data support iPCIT potential

Overall, the results support findings from previous studies of clinic-based PCIT for children with DD and previous studies of telehealth interventions for typically developing children, the researchers said.

“Moreover, iPCIT-treated children not only showed reductions in behavior problems, such as aggression, but demonstrated higher rates of following directions, which is especially important for children entering kindergarten,” they wrote.

The findings were limited by several factors including the narrow focus on the primary and secondary outcomes, the use of data from a single site in a single metropolitan area – which may limit generalizability – and the lack of comparison between iPCIT and a clinic-based PCIT control group, the researchers noted. The equipment in the current study was provided to families; therefore, differences in treatment response could not be attributed to differences in technology.

The study represents the first known randomized controlled trial to evaluate a telehealth parenting intervention for children with, according to the researchers. The results suggest that technology can be leveraged to help these patients, including those from ethnic minority families who may be underserved by clinic-based care in overcoming barriers to treatment such as transportation and availability of clinicians. Use of iPCIT could be a critical resource as young children with DD complete Part C services and enter the school system.
 

Practical pediatric takeaways

“This was a great study, well-designed and very important and helpful for pediatric providers,” Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Young children with developmental delay and/or mental and behavioral health disorders require early identification and intervention,” said Dr. Haut. However, obstacles to intervention include stigma or parental denial of the disorder, as well as more practical challenges related to transportation, time to access a clinic or office, potential long length of treatment, and cost.

“Despite availability of state programs for young children, follow up and continued services can be challenging to complete. Once the child outgrows the state program finding alternative therapy can be difficult with the current shortage of pediatric mental health providers,” Dr. Haut noted.

“I was surprised to see that this study treatment phase was completed prior to the COVID-19 pandemic, when telehealth was not as popular a mode for health care and was not utilized to the extent that it is now, especially for pediatric care,” said Dr. Haut. “I was not surprised at the results, as the traditional mode of PCIT includes therapy and training in a space that may not be as familiar to the child as their home environment, and would include live presence of the therapist/s, which may add to anxiety for both the parent and child.”

That almost half of the parents participating in the study had graduated from college and/or completed graduate degrees “may have contributed to some of the success of this study,” Dr. Haut noted.
 

Benefits and barriers

“The COVID-19 pandemic brought significant change to the frequency of use and overall success of telehealth services,” Dr. Haut said. “Additional provider education in aspects such as provider technique and the use of medical devices with improved specific health care technology assisted in advancing the experience and opportunity for successful telehealth visits. Telehealth therapy offers a cost-effective option for any pediatric patients and for providers, as the time and space commitment for the patient visit can be considerably less than live office visits.

“Unfortunately, there are still overall barriers that I have personally experienced with telehealth, including interruptions in connectivity, background noise, and lack of an available computer or tablet; and with the use of cell phones not always allowing full inclusion of the caregiver and child,” said Dr. Haut. Children with DD, behavioral problems, or other mental health disorders may pose challenges for parents to manage at home while simultaneously trying to fully focus on the therapy in an online setting.

Although the current study is encouraging, “larger studies focused on specific or individual pediatric mental health and/or behavioral disorders may offer more information for providers, and better document the success of telehealth delivery of services,” Dr. Haut said.

The study was supported by the National Institute of Child Health and Human Development. Dr. Bagner disclosed funding from the National Institutes of Health. He also disclosed personal fees from PCIT International to train clinicians in PCIT supported by a grant from the Florida Department of Children and Families outside the current study. Dr. Haut had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.

Telehealth parent-child interaction therapy improved the behavior of 3-year-olds with developmental delay in a randomized controlled trial.

The children received the therapy with their parents or caregivers, who were more likely to demonstrate positive parenting behaviors than parents in the control group, authors of the new research published in JAMA Pediatrics found.

Approximately 13% of children have some form of developmental delay (DD) and more than half of these children also have at least one mental health disorder, which makes behavior problems a common and ongoing challenge, Daniel M. Bagner, PhD, a psychologist at Florida International University, Miami, and colleagues wrote.

Clinic-based interventions such as parent-child interaction therapy (PCIT) have been effective for improving behavior in children with DD, the researchers said. PCIT involves in-session caregiver coaching using a 1-way mirror and a wireless earpiece worn by the caregiver.

Barriers to the use of PCIT, especially in marginalized and low-income communities, include transportation, clinician shortages, and stigma-related concerns about a clinic visit, the researchers wrote. Technology now allows for Internet-delivered PCIT to reach more children and families, but its effectiveness for children with DD has not been well studied.

In the new study, the researchers randomized 150 children with DD and externalizing behavior problems to up to 20 weeks of Internet-delivered parent-child interaction therapy (iPCIT) or to referral as usual (RAU, the control group). The children were randomized after completion of early intervention services within 3 months of their third birthday, and participated in the sessions with a parent or caregiver. Most of the participants were from economically disadvantaged households and underrepresented ethnic backgrounds.

The iPCIT intervention was conducted weekly with a remote therapist and lasted for 1-1.5 hours; approximately half of the families received the intervention in Spanish.

The primary outcome was rating on the Child Behavior Checklist (CBCL) and assessment of children and caregivers using the Dyadic Parent-Child Interaction Coding System, fourth edition (DPICS). Assessments occurred at baseline and at week 20 (post treatment), with follow ups at 6 and 12 months.

Scores on the CBCL in the iPCIT group decreased from a mean of 61.18 at baseline to 53.83 post intervention. Scores for the control group started at 64.05 and decreased to 59.49 post intervention. At 6-12 months, the scores for both groups remained stable.

Children who received iPCIT with their parent or caregiver also showed significantly lower levels of externalizing behavior problems, compared with the RAU controls post treatment, and at 6-month and 12-month follow-ups based on the Cohen d measure of standardized effect size for differences between groups.

Significantly more children in the iPCIT group showed clinically significant improvements in externalizing problems at post treatment, compared with the RAU group (74% vs. 42%; P < .001) and at 6 months’ follow-up (73% vs. 45%; P = .002). However, the differences from baseline were not significantly different between the two groups after 12 months, which suggests that the effects may wane over time, the researchers noted.

In addition, the rate of child compliance with parent commands, as measured by a cleanup task, approximately doubled by the 12-month follow-up among children in the iPCIT group versus an increase of approximately one-third in the RAU group.

For secondary outcome measures related to caregiver behaviors, the proportion of observed positive parenting behaviors increased in the iPCIT group during the course of the intervention (postintervention odds ratio, 1.10), and the proportion of controlling and critical behaviors decreased (postintervention OR, 1.40). Harsh and inconsistent discipline decreased in both groups based on self-reports, but the decrease was steeper in iPCIT families.

iPCIT did not have a greater impact than RAU in reducing caregiver stress. The researchers wrote that they were not surprised by the lack of stress reduction “given mixed findings on the impact of parenting interventions on stress in caregivers of children with DD.”
 

Data support iPCIT potential

Overall, the results support findings from previous studies of clinic-based PCIT for children with DD and previous studies of telehealth interventions for typically developing children, the researchers said.

“Moreover, iPCIT-treated children not only showed reductions in behavior problems, such as aggression, but demonstrated higher rates of following directions, which is especially important for children entering kindergarten,” they wrote.

The findings were limited by several factors including the narrow focus on the primary and secondary outcomes, the use of data from a single site in a single metropolitan area – which may limit generalizability – and the lack of comparison between iPCIT and a clinic-based PCIT control group, the researchers noted. The equipment in the current study was provided to families; therefore, differences in treatment response could not be attributed to differences in technology.

The study represents the first known randomized controlled trial to evaluate a telehealth parenting intervention for children with, according to the researchers. The results suggest that technology can be leveraged to help these patients, including those from ethnic minority families who may be underserved by clinic-based care in overcoming barriers to treatment such as transportation and availability of clinicians. Use of iPCIT could be a critical resource as young children with DD complete Part C services and enter the school system.
 

Practical pediatric takeaways

“This was a great study, well-designed and very important and helpful for pediatric providers,” Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Young children with developmental delay and/or mental and behavioral health disorders require early identification and intervention,” said Dr. Haut. However, obstacles to intervention include stigma or parental denial of the disorder, as well as more practical challenges related to transportation, time to access a clinic or office, potential long length of treatment, and cost.

“Despite availability of state programs for young children, follow up and continued services can be challenging to complete. Once the child outgrows the state program finding alternative therapy can be difficult with the current shortage of pediatric mental health providers,” Dr. Haut noted.

“I was surprised to see that this study treatment phase was completed prior to the COVID-19 pandemic, when telehealth was not as popular a mode for health care and was not utilized to the extent that it is now, especially for pediatric care,” said Dr. Haut. “I was not surprised at the results, as the traditional mode of PCIT includes therapy and training in a space that may not be as familiar to the child as their home environment, and would include live presence of the therapist/s, which may add to anxiety for both the parent and child.”

That almost half of the parents participating in the study had graduated from college and/or completed graduate degrees “may have contributed to some of the success of this study,” Dr. Haut noted.
 

Benefits and barriers

“The COVID-19 pandemic brought significant change to the frequency of use and overall success of telehealth services,” Dr. Haut said. “Additional provider education in aspects such as provider technique and the use of medical devices with improved specific health care technology assisted in advancing the experience and opportunity for successful telehealth visits. Telehealth therapy offers a cost-effective option for any pediatric patients and for providers, as the time and space commitment for the patient visit can be considerably less than live office visits.

“Unfortunately, there are still overall barriers that I have personally experienced with telehealth, including interruptions in connectivity, background noise, and lack of an available computer or tablet; and with the use of cell phones not always allowing full inclusion of the caregiver and child,” said Dr. Haut. Children with DD, behavioral problems, or other mental health disorders may pose challenges for parents to manage at home while simultaneously trying to fully focus on the therapy in an online setting.

Although the current study is encouraging, “larger studies focused on specific or individual pediatric mental health and/or behavioral disorders may offer more information for providers, and better document the success of telehealth delivery of services,” Dr. Haut said.

The study was supported by the National Institute of Child Health and Human Development. Dr. Bagner disclosed funding from the National Institutes of Health. He also disclosed personal fees from PCIT International to train clinicians in PCIT supported by a grant from the Florida Department of Children and Families outside the current study. Dr. Haut had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.

Almost one-third of patients with chronic pain report using medical cannabis to manage that pain, with more than half of them decreasing use of other pain medications, including opioids, new research shows.

“That patients report substituting cannabis for pain medicines so much really underscores the need for research on the benefits and risks of using cannabis for chronic pain,” lead author Mark C. Bicket, MD, PhD, assistant professor, department of anesthesiology, and director, Opioid Prescribing Engagement Network, University of Michigan, Ann Arbor, said in an interview.

However, he added, the question is whether they’re turning to cannabis and away from other pain treatments. “What’s not clear and one of the gaps that we wanted to address in the study was if medical cannabis use is changing the use of other treatments for chronic pain,” said Dr. Bicket.

The study was published online in JAMA Network Open.
 

Decreased opioid use

The survey included a representative sample of 1724 American adults aged 18 years or older with chronic noncancer pain living in areas with a medical cannabis program.

Respondents were asked about their use of three categories of pain treatments. This included medical cannabis; pharmacologic treatments including prescription opioids, nonopioid analgesics, and over-the-counter analgesics; and common nonpharmacologic treatments such as physical therapy, meditation, and cognitive-behavioral therapy (CBT).

Just over 96% of respondents completed the full survey. About 57% of the sample was female and the mean age of the study sample was 52.3 years.

Among study participants, 31% (95% CI, 28.2% - 34.1%) reported having ever used cannabis to manage pain; 25.9% (95% confidence interval, 23.2%-28.8%) reported use in the past 12 months, and 23.2% (95% CI, 20.6%-26%) reported use in the past 30 days.

“This translates into a large number of individuals who are using cannabis in an intended medical way” to treat chronic condition such as low back pain, migraine, and fibromyalgia, said Dr. Bicket.

More than half of survey respondents reported their medical cannabis use led to a decrease in prescription opioid use, prescription nonopioid use and use of over-the-counter medications.

Dr. Bicket noted “almost no one” said medical cannabis use led to higher use of these drugs.

As for nonpharmacologic treatments, 38.7% reported their use of cannabis led to decreased use of physical therapy, 19.1% to lower use of meditation, and 26% to less CBT. At the same time, 5.9%, 23.7% and 17.1%, respectively, reported it led to increased use of physical therapy, meditation, and CBT.

Medical cannabis is regulated at a state level. On a federal level, it’s considered a Schedule I substance, which means it’s deemed not to have a therapeutic use, although some groups are trying to change that categorization, said Dr. Bicket.

As a result, cannabis products “are quite variable” in terms of how they’re used (smoked, eaten etc.) and in their composition, including percentage of cannabidiol and tetrahydrocannabinol.

“We really don’t have a good sense of the relative risks and benefits that could come from cannabis as a treatment for chronic pain,” said Dr. Bicket. “As a physician, it’s difficult to have discussions with patients because I’m not able to understand the products they’re using based on this regulatory environment we have.”

He added clinicians “are operating in an area of uncertainty right now.”

What’s needed is research to determine how safe and effective medical cannabis is for chronic pain, he said.
 

Pain a leading indication

Commenting on the findings, Jason W. Busse, PhD, professor, department of anesthesia, and associate director, Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ont., said the study reinforces results of some prior research.

“It gives us current information certainly highlighting the high rate of use of medical cannabis among individuals with chronic pain once it becomes legally available.”

In addition, this high rate of use “means we desperately need information about the benefits and harms” of medical marijuana, he said.

Dr. Busse noted the survey didn’t provide information on the types of cannabis being used or the mode of administration. Oil drops and sprays cause less pulmonary harm than smoked versions, he said. It’s also not clear from the survey if participants are taking formulations with high levels of tetrahydrocannabinol that are associated with greater risk of harm.

He noted cannabis may interact with prescription drugs to make them less effective or, in some cases, to augment their adverse effects.

Dr. Busse pointed out some patients could be using fewer opioids because providers are under “enormous pressure” to reduce prescriptions of these drugs in the wake of spikes in opioid overdoses and deaths.

Chronic pain is “absolutely the leading indication” for medical marijuana, said Dr. Busse. U.S. reimbursement data suggest up to 65% of individuals get cannabis to treat a listed indication for chronic pain.

He said he hopes this new study will increase interest in funding new trials “so we can have better evidence to guide practice to help patients make decisions.”

The study received support from the National Institute on Drug Abuse. Dr. Bicket reported receiving personal fees from Axial Healthcare as well as grants from the National Institutes of Health, the Centers for Disease Control and Prevention, Michigan Department of Health and Human Services, Arnold Foundation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Dr. Busse reported no relevant financial relationships.

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

Almost one-third of patients with chronic pain report using medical cannabis to manage that pain, with more than half of them decreasing use of other pain medications, including opioids, new research shows.

“That patients report substituting cannabis for pain medicines so much really underscores the need for research on the benefits and risks of using cannabis for chronic pain,” lead author Mark C. Bicket, MD, PhD, assistant professor, department of anesthesiology, and director, Opioid Prescribing Engagement Network, University of Michigan, Ann Arbor, said in an interview.

However, he added, the question is whether they’re turning to cannabis and away from other pain treatments. “What’s not clear and one of the gaps that we wanted to address in the study was if medical cannabis use is changing the use of other treatments for chronic pain,” said Dr. Bicket.

The study was published online in JAMA Network Open.
 

Decreased opioid use

The survey included a representative sample of 1724 American adults aged 18 years or older with chronic noncancer pain living in areas with a medical cannabis program.

Respondents were asked about their use of three categories of pain treatments. This included medical cannabis; pharmacologic treatments including prescription opioids, nonopioid analgesics, and over-the-counter analgesics; and common nonpharmacologic treatments such as physical therapy, meditation, and cognitive-behavioral therapy (CBT).

Just over 96% of respondents completed the full survey. About 57% of the sample was female and the mean age of the study sample was 52.3 years.

Among study participants, 31% (95% CI, 28.2% - 34.1%) reported having ever used cannabis to manage pain; 25.9% (95% confidence interval, 23.2%-28.8%) reported use in the past 12 months, and 23.2% (95% CI, 20.6%-26%) reported use in the past 30 days.

“This translates into a large number of individuals who are using cannabis in an intended medical way” to treat chronic condition such as low back pain, migraine, and fibromyalgia, said Dr. Bicket.

More than half of survey respondents reported their medical cannabis use led to a decrease in prescription opioid use, prescription nonopioid use and use of over-the-counter medications.

Dr. Bicket noted “almost no one” said medical cannabis use led to higher use of these drugs.

As for nonpharmacologic treatments, 38.7% reported their use of cannabis led to decreased use of physical therapy, 19.1% to lower use of meditation, and 26% to less CBT. At the same time, 5.9%, 23.7% and 17.1%, respectively, reported it led to increased use of physical therapy, meditation, and CBT.

Medical cannabis is regulated at a state level. On a federal level, it’s considered a Schedule I substance, which means it’s deemed not to have a therapeutic use, although some groups are trying to change that categorization, said Dr. Bicket.

As a result, cannabis products “are quite variable” in terms of how they’re used (smoked, eaten etc.) and in their composition, including percentage of cannabidiol and tetrahydrocannabinol.

“We really don’t have a good sense of the relative risks and benefits that could come from cannabis as a treatment for chronic pain,” said Dr. Bicket. “As a physician, it’s difficult to have discussions with patients because I’m not able to understand the products they’re using based on this regulatory environment we have.”

He added clinicians “are operating in an area of uncertainty right now.”

What’s needed is research to determine how safe and effective medical cannabis is for chronic pain, he said.
 

Pain a leading indication

Commenting on the findings, Jason W. Busse, PhD, professor, department of anesthesia, and associate director, Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ont., said the study reinforces results of some prior research.

“It gives us current information certainly highlighting the high rate of use of medical cannabis among individuals with chronic pain once it becomes legally available.”

In addition, this high rate of use “means we desperately need information about the benefits and harms” of medical marijuana, he said.

Dr. Busse noted the survey didn’t provide information on the types of cannabis being used or the mode of administration. Oil drops and sprays cause less pulmonary harm than smoked versions, he said. It’s also not clear from the survey if participants are taking formulations with high levels of tetrahydrocannabinol that are associated with greater risk of harm.

He noted cannabis may interact with prescription drugs to make them less effective or, in some cases, to augment their adverse effects.

Dr. Busse pointed out some patients could be using fewer opioids because providers are under “enormous pressure” to reduce prescriptions of these drugs in the wake of spikes in opioid overdoses and deaths.

Chronic pain is “absolutely the leading indication” for medical marijuana, said Dr. Busse. U.S. reimbursement data suggest up to 65% of individuals get cannabis to treat a listed indication for chronic pain.

He said he hopes this new study will increase interest in funding new trials “so we can have better evidence to guide practice to help patients make decisions.”

The study received support from the National Institute on Drug Abuse. Dr. Bicket reported receiving personal fees from Axial Healthcare as well as grants from the National Institutes of Health, the Centers for Disease Control and Prevention, Michigan Department of Health and Human Services, Arnold Foundation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Dr. Busse reported no relevant financial relationships.

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

Almost one-third of patients with chronic pain report using medical cannabis to manage that pain, with more than half of them decreasing use of other pain medications, including opioids, new research shows.

“That patients report substituting cannabis for pain medicines so much really underscores the need for research on the benefits and risks of using cannabis for chronic pain,” lead author Mark C. Bicket, MD, PhD, assistant professor, department of anesthesiology, and director, Opioid Prescribing Engagement Network, University of Michigan, Ann Arbor, said in an interview.

However, he added, the question is whether they’re turning to cannabis and away from other pain treatments. “What’s not clear and one of the gaps that we wanted to address in the study was if medical cannabis use is changing the use of other treatments for chronic pain,” said Dr. Bicket.

The study was published online in JAMA Network Open.
 

Decreased opioid use

The survey included a representative sample of 1724 American adults aged 18 years or older with chronic noncancer pain living in areas with a medical cannabis program.

Respondents were asked about their use of three categories of pain treatments. This included medical cannabis; pharmacologic treatments including prescription opioids, nonopioid analgesics, and over-the-counter analgesics; and common nonpharmacologic treatments such as physical therapy, meditation, and cognitive-behavioral therapy (CBT).

Just over 96% of respondents completed the full survey. About 57% of the sample was female and the mean age of the study sample was 52.3 years.

Among study participants, 31% (95% CI, 28.2% - 34.1%) reported having ever used cannabis to manage pain; 25.9% (95% confidence interval, 23.2%-28.8%) reported use in the past 12 months, and 23.2% (95% CI, 20.6%-26%) reported use in the past 30 days.

“This translates into a large number of individuals who are using cannabis in an intended medical way” to treat chronic condition such as low back pain, migraine, and fibromyalgia, said Dr. Bicket.

More than half of survey respondents reported their medical cannabis use led to a decrease in prescription opioid use, prescription nonopioid use and use of over-the-counter medications.

Dr. Bicket noted “almost no one” said medical cannabis use led to higher use of these drugs.

As for nonpharmacologic treatments, 38.7% reported their use of cannabis led to decreased use of physical therapy, 19.1% to lower use of meditation, and 26% to less CBT. At the same time, 5.9%, 23.7% and 17.1%, respectively, reported it led to increased use of physical therapy, meditation, and CBT.

Medical cannabis is regulated at a state level. On a federal level, it’s considered a Schedule I substance, which means it’s deemed not to have a therapeutic use, although some groups are trying to change that categorization, said Dr. Bicket.

As a result, cannabis products “are quite variable” in terms of how they’re used (smoked, eaten etc.) and in their composition, including percentage of cannabidiol and tetrahydrocannabinol.

“We really don’t have a good sense of the relative risks and benefits that could come from cannabis as a treatment for chronic pain,” said Dr. Bicket. “As a physician, it’s difficult to have discussions with patients because I’m not able to understand the products they’re using based on this regulatory environment we have.”

He added clinicians “are operating in an area of uncertainty right now.”

What’s needed is research to determine how safe and effective medical cannabis is for chronic pain, he said.
 

Pain a leading indication

Commenting on the findings, Jason W. Busse, PhD, professor, department of anesthesia, and associate director, Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ont., said the study reinforces results of some prior research.

“It gives us current information certainly highlighting the high rate of use of medical cannabis among individuals with chronic pain once it becomes legally available.”

In addition, this high rate of use “means we desperately need information about the benefits and harms” of medical marijuana, he said.

Dr. Busse noted the survey didn’t provide information on the types of cannabis being used or the mode of administration. Oil drops and sprays cause less pulmonary harm than smoked versions, he said. It’s also not clear from the survey if participants are taking formulations with high levels of tetrahydrocannabinol that are associated with greater risk of harm.

He noted cannabis may interact with prescription drugs to make them less effective or, in some cases, to augment their adverse effects.

Dr. Busse pointed out some patients could be using fewer opioids because providers are under “enormous pressure” to reduce prescriptions of these drugs in the wake of spikes in opioid overdoses and deaths.

Chronic pain is “absolutely the leading indication” for medical marijuana, said Dr. Busse. U.S. reimbursement data suggest up to 65% of individuals get cannabis to treat a listed indication for chronic pain.

He said he hopes this new study will increase interest in funding new trials “so we can have better evidence to guide practice to help patients make decisions.”

The study received support from the National Institute on Drug Abuse. Dr. Bicket reported receiving personal fees from Axial Healthcare as well as grants from the National Institutes of Health, the Centers for Disease Control and Prevention, Michigan Department of Health and Human Services, Arnold Foundation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Dr. Busse reported no relevant financial relationships.

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

Attention-deficit/hyperactivity disorder (ADHD) is often a very challenging condition for parents to manage, both because of the “gleeful mayhem” children with ADHD manifest and because of the nature of effective treatments. Multiple randomized controlled studies and meta-analyses have demonstrated that stimulant medication with behavioral interventions is the optimal first-line treatment for children with both subtypes of ADHD, and that medications alone are superior to behavioral interventions alone. By improving attention and impulse control, the medications effectively decrease the many negative interactions with teachers, peers, and parents, aiding development and healthy self-esteem.

But many parents feel anxious about treating their young children with stimulants. Importantly, how children with ADHD will fare as adults is not predicted by their symptom level, but instead by the quality of their relationships with their parents, their ability to perform at school, and their social skills. Bring this framework to parents as you listen to their questions and help them decide on the best approach for their family. To assist you in these conversations, we will review the evidence for (or against) several of the most common alternatives to medication that parents are likely to ask about.
 

Diets and supplements

Dietary modifications are among the most popular “natural” approaches to managing ADHD in children. Diets that eliminate processed sugars or food additives (particularly artificial food coloring) are among the most common approaches discussed in the lay press. These diets are usually very time-consuming and disruptive for families to follow, and there is no evidence to support their general use in ADHD management. Those studies that rigorously examined them suggest that, for children with severe impairment who have failed to respond to medications for ADHD, a workup for food intolerance or nutritional deficits may reveal a different problem underlying their behavioral difficulties.¹

Similarly, supplementation with high-dose omega-3 fatty acids is modestly helpful only in a subset of children with ADHD symptoms, and not nearly as effective as medications or behavioral interventions. Spending time on an exacting diet or buying expensive supplements is very unlikely to relieve the children’s symptoms and may only add to their stress at home. The “sugar high” parents note may be the rare joy of eating a candy bar and not sugar causing ADHD. Offer parents the guidance to focus on a healthy diet, high in fruits and vegetables, whole grains, and healthy protein, and on meals that emphasize family time instead of struggles around food.
 

Neurofeedback

Neurofeedback is an approach that grew out of the observation that many adults with ADHD had resting patterns of brain wave activity different from those of neurotypical adults. In neurofeedback, patients learn strategies that amplify the brain waves associated with focused mental activity, rather than listless or hyperactive states. Businesses market this service for all sorts of illnesses and challenges, ADHD chief among them. Despite the marketing, there are very few randomized controlled studies of this intervention for ADHD in youth, and those have shown only the possibility of a benefit.

While there is no evidence of serious side effects, these treatments are time-consuming and expensive and unlikely to be covered by any insurance. You might suggest to parents that they could achieve some of the same theoretical benefits by looking for hobbies that invite sustained focus in their children. That is, they should think about activities that interest the children, such as music lessons or karate, that they could practice in classes and at home. If the children find these activities even somewhat interesting (or just enjoy the reward of their parents’ or teachers’ attention), regular practice will be supporting their developing attention while building social skills and authentic self-confidence, rather than the activities feeling like a treatment for an illness or condition.

Sleep and exercise

There are not many businesses or books selling worried and exhausted parents a quick nonmedication solution for their children’s ADHD in the form of healthy sleep and exercise habits. But these are safe and healthy ways to reduce symptoms and support development. Children with ADHD often enjoy and benefit from participating in a sport, and daily exercise can help with sleep and regulating their energy. They also often have difficulty with sleep initiation, and commonly do not get adequate or restful sleep. Inadequate sleep exacerbates inattention, distractibility, and irritability. Children with untreated ADHD also often spend a lot of time on screens, as it is difficult for them to shift away from rewarding activities, and parents can find screen time to be a welcome break from hyperactivity and negative interactions. But excessive screen time, especially close to bedtime, can worsen irritability and make sleep more difficult. Talk with parents about the value of establishing a routine around screen time, modest daily physical activity, and sleep that everyone can follow. If their family life is currently marked by late bedtimes and long hours in front of video games, this change will take effort. But within a few weeks, it could lead to significant improvements in energy, attention, and interactions at home.

Behavioral treatments

Effective behavioral treatments for ADHD do not change ADHD symptoms, but they do help children learn how to manage them. In “parent management training,” younger children and parents learn together how to avoid negative cycles of behavior (i.e., temper outbursts) by focusing on consistent routines and consequences that support children calmly learning to manage their impulses. The only other evidence-based treatment focuses on helping school age and older children develop executive functions – their planning, organization, and time management skills – with a range of age-appropriate tools. Both of these therapies may be more effective if the children are also receiving medication, but medication is not necessary for them to be helpful. It is important to note that play therapy and other evidence-based psychotherapies are not effective for management of ADHD, although they may treat comorbid problems.

Parent treatment

You may have diagnosed children with ADHD only to hear their parents respond by saying that they suspect (or know) that they (or their spouses) also have ADHD. This would not be surprising, as ADHD has one of the highest rates of heritability of psychiatric disorders, at 80%. Somewhere between 25% and 50% of parents of children with ADHD have ADHD themselves.² Screening for adults with ADHD, such as the Adult ADHD Self-Report Scale, is widely available and free. Speak with parents about the fact that behavioral treatments for their children’s ADHD are demanding. Such treatments require patience, calm, organization, and consistency.

If parents have ADHD, it may be very helpful for them to prioritize their own effective treatments, so that their attention and impulse control will support their parenting. They may be interested in learning about how treatment might also improve their performance at work and even the quality of their relationships. While there is some evidence that their children’s treatment outcome will hinge on the parents’ treatment,³ they deserve good care independent of the expectations of parenting.

Families benefit from a comprehensive “ADHD plan” for their children. This would start with an assessment of the severity of their children’s symptoms, specifying their impairment at home, school, and in social relationships. It would include their nonacademic performance, exploration of interests, and developing self-confidence. All of these considerations lead to setting reasonable expectations so the children can feel successful. Parents should think about how best to structure their children’s schedules to promote healthy sleep, exercise, and nutrition, and to expand opportunities for building their frustration tolerance, social skills, and executive function.

Parents will need to consider what kind of supports they themselves need to offer this structure. There are good resources available online for information and support, including Children and Adults with ADHD (chadd.org) and the ADHD Resource Center from the American Academy of Child and Adolescent Psychiatry (aacap.org). This approach may help parents to evaluate the potential risks and benefits of medications as a component of treatment. Most of the quick fixes for childhood ADHD on the market will take a family’s time and money without providing meaningful improvement. Parents should focus instead on the tried-and-true routines and supports that will help them to create the setting at home that will enable their children to flourish.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Millichap JG and Yee MM. Pediatrics. 2012 Feb;129(2):330-7.

2. Grimm O et al. Curr Psychiatry Rep. 2020 Feb 27;22(4):18.

3. Chronis-Tuscano A et al. J Abnorm Child Psychol. 2017 Apr;45(3):501-7.

Attention-deficit/hyperactivity disorder (ADHD) is often a very challenging condition for parents to manage, both because of the “gleeful mayhem” children with ADHD manifest and because of the nature of effective treatments. Multiple randomized controlled studies and meta-analyses have demonstrated that stimulant medication with behavioral interventions is the optimal first-line treatment for children with both subtypes of ADHD, and that medications alone are superior to behavioral interventions alone. By improving attention and impulse control, the medications effectively decrease the many negative interactions with teachers, peers, and parents, aiding development and healthy self-esteem.

But many parents feel anxious about treating their young children with stimulants. Importantly, how children with ADHD will fare as adults is not predicted by their symptom level, but instead by the quality of their relationships with their parents, their ability to perform at school, and their social skills. Bring this framework to parents as you listen to their questions and help them decide on the best approach for their family. To assist you in these conversations, we will review the evidence for (or against) several of the most common alternatives to medication that parents are likely to ask about.
 

Diets and supplements

Dietary modifications are among the most popular “natural” approaches to managing ADHD in children. Diets that eliminate processed sugars or food additives (particularly artificial food coloring) are among the most common approaches discussed in the lay press. These diets are usually very time-consuming and disruptive for families to follow, and there is no evidence to support their general use in ADHD management. Those studies that rigorously examined them suggest that, for children with severe impairment who have failed to respond to medications for ADHD, a workup for food intolerance or nutritional deficits may reveal a different problem underlying their behavioral difficulties.¹

Similarly, supplementation with high-dose omega-3 fatty acids is modestly helpful only in a subset of children with ADHD symptoms, and not nearly as effective as medications or behavioral interventions. Spending time on an exacting diet or buying expensive supplements is very unlikely to relieve the children’s symptoms and may only add to their stress at home. The “sugar high” parents note may be the rare joy of eating a candy bar and not sugar causing ADHD. Offer parents the guidance to focus on a healthy diet, high in fruits and vegetables, whole grains, and healthy protein, and on meals that emphasize family time instead of struggles around food.
 

Neurofeedback

Neurofeedback is an approach that grew out of the observation that many adults with ADHD had resting patterns of brain wave activity different from those of neurotypical adults. In neurofeedback, patients learn strategies that amplify the brain waves associated with focused mental activity, rather than listless or hyperactive states. Businesses market this service for all sorts of illnesses and challenges, ADHD chief among them. Despite the marketing, there are very few randomized controlled studies of this intervention for ADHD in youth, and those have shown only the possibility of a benefit.

While there is no evidence of serious side effects, these treatments are time-consuming and expensive and unlikely to be covered by any insurance. You might suggest to parents that they could achieve some of the same theoretical benefits by looking for hobbies that invite sustained focus in their children. That is, they should think about activities that interest the children, such as music lessons or karate, that they could practice in classes and at home. If the children find these activities even somewhat interesting (or just enjoy the reward of their parents’ or teachers’ attention), regular practice will be supporting their developing attention while building social skills and authentic self-confidence, rather than the activities feeling like a treatment for an illness or condition.

Sleep and exercise

There are not many businesses or books selling worried and exhausted parents a quick nonmedication solution for their children’s ADHD in the form of healthy sleep and exercise habits. But these are safe and healthy ways to reduce symptoms and support development. Children with ADHD often enjoy and benefit from participating in a sport, and daily exercise can help with sleep and regulating their energy. They also often have difficulty with sleep initiation, and commonly do not get adequate or restful sleep. Inadequate sleep exacerbates inattention, distractibility, and irritability. Children with untreated ADHD also often spend a lot of time on screens, as it is difficult for them to shift away from rewarding activities, and parents can find screen time to be a welcome break from hyperactivity and negative interactions. But excessive screen time, especially close to bedtime, can worsen irritability and make sleep more difficult. Talk with parents about the value of establishing a routine around screen time, modest daily physical activity, and sleep that everyone can follow. If their family life is currently marked by late bedtimes and long hours in front of video games, this change will take effort. But within a few weeks, it could lead to significant improvements in energy, attention, and interactions at home.

Behavioral treatments

Effective behavioral treatments for ADHD do not change ADHD symptoms, but they do help children learn how to manage them. In “parent management training,” younger children and parents learn together how to avoid negative cycles of behavior (i.e., temper outbursts) by focusing on consistent routines and consequences that support children calmly learning to manage their impulses. The only other evidence-based treatment focuses on helping school age and older children develop executive functions – their planning, organization, and time management skills – with a range of age-appropriate tools. Both of these therapies may be more effective if the children are also receiving medication, but medication is not necessary for them to be helpful. It is important to note that play therapy and other evidence-based psychotherapies are not effective for management of ADHD, although they may treat comorbid problems.

Parent treatment

You may have diagnosed children with ADHD only to hear their parents respond by saying that they suspect (or know) that they (or their spouses) also have ADHD. This would not be surprising, as ADHD has one of the highest rates of heritability of psychiatric disorders, at 80%. Somewhere between 25% and 50% of parents of children with ADHD have ADHD themselves.² Screening for adults with ADHD, such as the Adult ADHD Self-Report Scale, is widely available and free. Speak with parents about the fact that behavioral treatments for their children’s ADHD are demanding. Such treatments require patience, calm, organization, and consistency.

If parents have ADHD, it may be very helpful for them to prioritize their own effective treatments, so that their attention and impulse control will support their parenting. They may be interested in learning about how treatment might also improve their performance at work and even the quality of their relationships. While there is some evidence that their children’s treatment outcome will hinge on the parents’ treatment,³ they deserve good care independent of the expectations of parenting.

Families benefit from a comprehensive “ADHD plan” for their children. This would start with an assessment of the severity of their children’s symptoms, specifying their impairment at home, school, and in social relationships. It would include their nonacademic performance, exploration of interests, and developing self-confidence. All of these considerations lead to setting reasonable expectations so the children can feel successful. Parents should think about how best to structure their children’s schedules to promote healthy sleep, exercise, and nutrition, and to expand opportunities for building their frustration tolerance, social skills, and executive function.

Parents will need to consider what kind of supports they themselves need to offer this structure. There are good resources available online for information and support, including Children and Adults with ADHD (chadd.org) and the ADHD Resource Center from the American Academy of Child and Adolescent Psychiatry (aacap.org). This approach may help parents to evaluate the potential risks and benefits of medications as a component of treatment. Most of the quick fixes for childhood ADHD on the market will take a family’s time and money without providing meaningful improvement. Parents should focus instead on the tried-and-true routines and supports that will help them to create the setting at home that will enable their children to flourish.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Millichap JG and Yee MM. Pediatrics. 2012 Feb;129(2):330-7.

2. Grimm O et al. Curr Psychiatry Rep. 2020 Feb 27;22(4):18.

3. Chronis-Tuscano A et al. J Abnorm Child Psychol. 2017 Apr;45(3):501-7.

Attention-deficit/hyperactivity disorder (ADHD) is often a very challenging condition for parents to manage, both because of the “gleeful mayhem” children with ADHD manifest and because of the nature of effective treatments. Multiple randomized controlled studies and meta-analyses have demonstrated that stimulant medication with behavioral interventions is the optimal first-line treatment for children with both subtypes of ADHD, and that medications alone are superior to behavioral interventions alone. By improving attention and impulse control, the medications effectively decrease the many negative interactions with teachers, peers, and parents, aiding development and healthy self-esteem.

But many parents feel anxious about treating their young children with stimulants. Importantly, how children with ADHD will fare as adults is not predicted by their symptom level, but instead by the quality of their relationships with their parents, their ability to perform at school, and their social skills. Bring this framework to parents as you listen to their questions and help them decide on the best approach for their family. To assist you in these conversations, we will review the evidence for (or against) several of the most common alternatives to medication that parents are likely to ask about.
 

Diets and supplements

Dietary modifications are among the most popular “natural” approaches to managing ADHD in children. Diets that eliminate processed sugars or food additives (particularly artificial food coloring) are among the most common approaches discussed in the lay press. These diets are usually very time-consuming and disruptive for families to follow, and there is no evidence to support their general use in ADHD management. Those studies that rigorously examined them suggest that, for children with severe impairment who have failed to respond to medications for ADHD, a workup for food intolerance or nutritional deficits may reveal a different problem underlying their behavioral difficulties.¹

Similarly, supplementation with high-dose omega-3 fatty acids is modestly helpful only in a subset of children with ADHD symptoms, and not nearly as effective as medications or behavioral interventions. Spending time on an exacting diet or buying expensive supplements is very unlikely to relieve the children’s symptoms and may only add to their stress at home. The “sugar high” parents note may be the rare joy of eating a candy bar and not sugar causing ADHD. Offer parents the guidance to focus on a healthy diet, high in fruits and vegetables, whole grains, and healthy protein, and on meals that emphasize family time instead of struggles around food.
 

Neurofeedback

Neurofeedback is an approach that grew out of the observation that many adults with ADHD had resting patterns of brain wave activity different from those of neurotypical adults. In neurofeedback, patients learn strategies that amplify the brain waves associated with focused mental activity, rather than listless or hyperactive states. Businesses market this service for all sorts of illnesses and challenges, ADHD chief among them. Despite the marketing, there are very few randomized controlled studies of this intervention for ADHD in youth, and those have shown only the possibility of a benefit.

While there is no evidence of serious side effects, these treatments are time-consuming and expensive and unlikely to be covered by any insurance. You might suggest to parents that they could achieve some of the same theoretical benefits by looking for hobbies that invite sustained focus in their children. That is, they should think about activities that interest the children, such as music lessons or karate, that they could practice in classes and at home. If the children find these activities even somewhat interesting (or just enjoy the reward of their parents’ or teachers’ attention), regular practice will be supporting their developing attention while building social skills and authentic self-confidence, rather than the activities feeling like a treatment for an illness or condition.

Sleep and exercise

There are not many businesses or books selling worried and exhausted parents a quick nonmedication solution for their children’s ADHD in the form of healthy sleep and exercise habits. But these are safe and healthy ways to reduce symptoms and support development. Children with ADHD often enjoy and benefit from participating in a sport, and daily exercise can help with sleep and regulating their energy. They also often have difficulty with sleep initiation, and commonly do not get adequate or restful sleep. Inadequate sleep exacerbates inattention, distractibility, and irritability. Children with untreated ADHD also often spend a lot of time on screens, as it is difficult for them to shift away from rewarding activities, and parents can find screen time to be a welcome break from hyperactivity and negative interactions. But excessive screen time, especially close to bedtime, can worsen irritability and make sleep more difficult. Talk with parents about the value of establishing a routine around screen time, modest daily physical activity, and sleep that everyone can follow. If their family life is currently marked by late bedtimes and long hours in front of video games, this change will take effort. But within a few weeks, it could lead to significant improvements in energy, attention, and interactions at home.

Behavioral treatments

Effective behavioral treatments for ADHD do not change ADHD symptoms, but they do help children learn how to manage them. In “parent management training,” younger children and parents learn together how to avoid negative cycles of behavior (i.e., temper outbursts) by focusing on consistent routines and consequences that support children calmly learning to manage their impulses. The only other evidence-based treatment focuses on helping school age and older children develop executive functions – their planning, organization, and time management skills – with a range of age-appropriate tools. Both of these therapies may be more effective if the children are also receiving medication, but medication is not necessary for them to be helpful. It is important to note that play therapy and other evidence-based psychotherapies are not effective for management of ADHD, although they may treat comorbid problems.

Parent treatment

You may have diagnosed children with ADHD only to hear their parents respond by saying that they suspect (or know) that they (or their spouses) also have ADHD. This would not be surprising, as ADHD has one of the highest rates of heritability of psychiatric disorders, at 80%. Somewhere between 25% and 50% of parents of children with ADHD have ADHD themselves.² Screening for adults with ADHD, such as the Adult ADHD Self-Report Scale, is widely available and free. Speak with parents about the fact that behavioral treatments for their children’s ADHD are demanding. Such treatments require patience, calm, organization, and consistency.

If parents have ADHD, it may be very helpful for them to prioritize their own effective treatments, so that their attention and impulse control will support their parenting. They may be interested in learning about how treatment might also improve their performance at work and even the quality of their relationships. While there is some evidence that their children’s treatment outcome will hinge on the parents’ treatment,³ they deserve good care independent of the expectations of parenting.

Families benefit from a comprehensive “ADHD plan” for their children. This would start with an assessment of the severity of their children’s symptoms, specifying their impairment at home, school, and in social relationships. It would include their nonacademic performance, exploration of interests, and developing self-confidence. All of these considerations lead to setting reasonable expectations so the children can feel successful. Parents should think about how best to structure their children’s schedules to promote healthy sleep, exercise, and nutrition, and to expand opportunities for building their frustration tolerance, social skills, and executive function.

Parents will need to consider what kind of supports they themselves need to offer this structure. There are good resources available online for information and support, including Children and Adults with ADHD (chadd.org) and the ADHD Resource Center from the American Academy of Child and Adolescent Psychiatry (aacap.org). This approach may help parents to evaluate the potential risks and benefits of medications as a component of treatment. Most of the quick fixes for childhood ADHD on the market will take a family’s time and money without providing meaningful improvement. Parents should focus instead on the tried-and-true routines and supports that will help them to create the setting at home that will enable their children to flourish.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Millichap JG and Yee MM. Pediatrics. 2012 Feb;129(2):330-7.

2. Grimm O et al. Curr Psychiatry Rep. 2020 Feb 27;22(4):18.

3. Chronis-Tuscano A et al. J Abnorm Child Psychol. 2017 Apr;45(3):501-7.

Adding a modified Atkins diet to standard antiseizure treatments significantly reduces seizure frequency in patients with drug-resistant epilepsy compared with medication alone, new research shows.

In a randomized prospective study, the number of seizures per month dropped by more than half in one-quarter of patients following the high-fat, low-carb diet; and 5% of the group were free from all seizure activity after 6 months.

Both adults and adolescents reported benefits from the diet, which is a less strict version of a traditional ketogenic diet that many patients find difficult to follow. The modified Atkins diet includes foods such as leafy green vegetables and eggs, chicken, fish, bacon, and other animal proteins.

“The use of an exchange list and recipe booklet with local recipes and spices helped in the initiation of modified Atkins diet with the flexibility of meal choices and ease of administration,” said coinvestigator Manjari Tripathi, MD, DM, department of neurology, All India Institute of Medical Science, New Delhi.

“As items were everyday household ingredients in proportion to the requirement of the modified Atkins diet, this diet is possible in low-income countries also,” Dr. Tripathi added.

The findings were published online in the journal Neurology.
 

Low carbs, high benefit

The modified Atkins diet includes around 65% fat, 25% protein, and 10% carbohydrates. Unlike a traditional ketogenic diet, the modified Atkins diet includes no restrictions on protein, calories, or fluids.

Researchers have long known that ketogenic and Atkins diets are associated with reduced seizure activity in adolescents with epilepsy. But previous studies were small, and many were retrospective analyses.

The current investigators enrolled 160 patients (80 adults, 80 adolescents) aged 10-55 years whose epilepsy was not controlled despite using at least three antiseizure medications at maximum tolerated doses.

The intervention group received training in the modified Atkins diet and were given a food exchange list, sample menu, and recipe booklet. Carbohydrate intake was restricted to 20 grams per day.

Participants took supplemental multivitamins and minerals, kept a food diary, logged seizure activity, and measured urine ketone levels three times a day. They also received weekly check-up phone calls to ensure diet adherence.

The control group received a normal diet with no carbohydrate restrictions. All participants continued their prescribed antiseizure therapy throughout the trial.
 

Primary outcome met

The primary study outcome was a reduction in seizures of more than 50%. At 6 months, 26.2% of the intervention group had reached that goal, compared with just 2.5% of the control group (P < .001).

When the median number of seizures in the modified Atkins diet group was analyzed, the frequency dropped in the intervention group from 37.5 per month at baseline to 27.5 per month after 3 months of the modified Atkins diet and to 21.5 per month after 6 months.

Adding the modified Atkins diet had a larger effect on seizure activity in adults than in adolescents. At the end of 6 months, 36% of adolescents on the modified Atkins diet had more than a 50% reduction in seizures, while 57.1% of adults on the diet reached that level.

Quality-of-life scores were also higher in the intervention group.

By the end of the trial, 5% of patients on the modified Atkins diet had no seizure activity at all versus none of the control group. In fact, the median number of seizures increased in the control group during the study.

The mean morning and evening levels of urine ketosis in the intervention group were 58.3 ± 8.0 mg/dL and 62.2 ± 22.6 mg/dL, respectively, suggesting satisfactory diet adherence. There was no significant difference between groups in weight loss.

Dr. Tripathi noted that 33% of participants did not complete the study because of poor tolerance of the diet, lack of benefit, or the inability to follow up – in part due to COVID-19. However, she said tolerance of the modified Atkins diet was better than what has been reported with the ketogenic diet.

“Though the exact mechanism by which such a diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influences the dynamics of the major inhibitory and excitatory neurotransmitter systems in the brain,” Dr. Tripathi said.
 

Benefits outweigh cost

Commenting on the research findings, Mackenzie Cervenka, MD, professor of neurology and director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore, noted that the study is the first randomized controlled trial of this size to demonstrate a benefit from adding the modified Atkins diet to standard antiseizure therapy in treatment-resistant epilepsy.

“Importantly, the study also showed improvement in quality of life and behavior over standard-of-care therapies without significant adverse effects,” said Dr. Cervenka, who was not part of the research.

The investigators noted that the flexibility of the modified Atkins diet allows more variation in menu options and a greater intake of protein, making it easier to follow than a traditional ketogenic diet.

One area of debate, however, is whether these diets are manageable for individuals with low income. Poultry, meat, and fish, all of which are staples of a modified Atkins diet, can be more expensive than other high-carb options such as pasta and rice.

“While some of the foods such as protein sources that patients purchase when they are on a ketogenic diet therapy can be more expensive, if you take into account the cost of antiseizure medications and other antiseizure treatments, hospital visits, and missed work related to seizures, et cetera, the overall financial benefits of seizure reduction with incorporating a ketogenic diet therapy may outweigh these costs,” Dr. Cervenka said.

“There are also low-cost foods that can be used since there is a great deal of flexibility with a modified Atkins diet,” she added.

The study was funded by the Centre of Excellence for Epilepsy, which is funded by the Department of Biotechnology, Government of India. Dr. Tripathi and Dr. Cervenka report no relevant financial relationships.

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

Adding a modified Atkins diet to standard antiseizure treatments significantly reduces seizure frequency in patients with drug-resistant epilepsy compared with medication alone, new research shows.

In a randomized prospective study, the number of seizures per month dropped by more than half in one-quarter of patients following the high-fat, low-carb diet; and 5% of the group were free from all seizure activity after 6 months.

Both adults and adolescents reported benefits from the diet, which is a less strict version of a traditional ketogenic diet that many patients find difficult to follow. The modified Atkins diet includes foods such as leafy green vegetables and eggs, chicken, fish, bacon, and other animal proteins.

“The use of an exchange list and recipe booklet with local recipes and spices helped in the initiation of modified Atkins diet with the flexibility of meal choices and ease of administration,” said coinvestigator Manjari Tripathi, MD, DM, department of neurology, All India Institute of Medical Science, New Delhi.

“As items were everyday household ingredients in proportion to the requirement of the modified Atkins diet, this diet is possible in low-income countries also,” Dr. Tripathi added.

The findings were published online in the journal Neurology.
 

Low carbs, high benefit

The modified Atkins diet includes around 65% fat, 25% protein, and 10% carbohydrates. Unlike a traditional ketogenic diet, the modified Atkins diet includes no restrictions on protein, calories, or fluids.

Researchers have long known that ketogenic and Atkins diets are associated with reduced seizure activity in adolescents with epilepsy. But previous studies were small, and many were retrospective analyses.

The current investigators enrolled 160 patients (80 adults, 80 adolescents) aged 10-55 years whose epilepsy was not controlled despite using at least three antiseizure medications at maximum tolerated doses.

The intervention group received training in the modified Atkins diet and were given a food exchange list, sample menu, and recipe booklet. Carbohydrate intake was restricted to 20 grams per day.

Participants took supplemental multivitamins and minerals, kept a food diary, logged seizure activity, and measured urine ketone levels three times a day. They also received weekly check-up phone calls to ensure diet adherence.

The control group received a normal diet with no carbohydrate restrictions. All participants continued their prescribed antiseizure therapy throughout the trial.
 

Primary outcome met

The primary study outcome was a reduction in seizures of more than 50%. At 6 months, 26.2% of the intervention group had reached that goal, compared with just 2.5% of the control group (P < .001).

When the median number of seizures in the modified Atkins diet group was analyzed, the frequency dropped in the intervention group from 37.5 per month at baseline to 27.5 per month after 3 months of the modified Atkins diet and to 21.5 per month after 6 months.

Adding the modified Atkins diet had a larger effect on seizure activity in adults than in adolescents. At the end of 6 months, 36% of adolescents on the modified Atkins diet had more than a 50% reduction in seizures, while 57.1% of adults on the diet reached that level.

Quality-of-life scores were also higher in the intervention group.

By the end of the trial, 5% of patients on the modified Atkins diet had no seizure activity at all versus none of the control group. In fact, the median number of seizures increased in the control group during the study.

The mean morning and evening levels of urine ketosis in the intervention group were 58.3 ± 8.0 mg/dL and 62.2 ± 22.6 mg/dL, respectively, suggesting satisfactory diet adherence. There was no significant difference between groups in weight loss.

Dr. Tripathi noted that 33% of participants did not complete the study because of poor tolerance of the diet, lack of benefit, or the inability to follow up – in part due to COVID-19. However, she said tolerance of the modified Atkins diet was better than what has been reported with the ketogenic diet.

“Though the exact mechanism by which such a diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influences the dynamics of the major inhibitory and excitatory neurotransmitter systems in the brain,” Dr. Tripathi said.
 

Benefits outweigh cost

Commenting on the research findings, Mackenzie Cervenka, MD, professor of neurology and director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore, noted that the study is the first randomized controlled trial of this size to demonstrate a benefit from adding the modified Atkins diet to standard antiseizure therapy in treatment-resistant epilepsy.

“Importantly, the study also showed improvement in quality of life and behavior over standard-of-care therapies without significant adverse effects,” said Dr. Cervenka, who was not part of the research.

The investigators noted that the flexibility of the modified Atkins diet allows more variation in menu options and a greater intake of protein, making it easier to follow than a traditional ketogenic diet.

One area of debate, however, is whether these diets are manageable for individuals with low income. Poultry, meat, and fish, all of which are staples of a modified Atkins diet, can be more expensive than other high-carb options such as pasta and rice.

“While some of the foods such as protein sources that patients purchase when they are on a ketogenic diet therapy can be more expensive, if you take into account the cost of antiseizure medications and other antiseizure treatments, hospital visits, and missed work related to seizures, et cetera, the overall financial benefits of seizure reduction with incorporating a ketogenic diet therapy may outweigh these costs,” Dr. Cervenka said.

“There are also low-cost foods that can be used since there is a great deal of flexibility with a modified Atkins diet,” she added.

The study was funded by the Centre of Excellence for Epilepsy, which is funded by the Department of Biotechnology, Government of India. Dr. Tripathi and Dr. Cervenka report no relevant financial relationships.

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

Adding a modified Atkins diet to standard antiseizure treatments significantly reduces seizure frequency in patients with drug-resistant epilepsy compared with medication alone, new research shows.

In a randomized prospective study, the number of seizures per month dropped by more than half in one-quarter of patients following the high-fat, low-carb diet; and 5% of the group were free from all seizure activity after 6 months.

Both adults and adolescents reported benefits from the diet, which is a less strict version of a traditional ketogenic diet that many patients find difficult to follow. The modified Atkins diet includes foods such as leafy green vegetables and eggs, chicken, fish, bacon, and other animal proteins.

“The use of an exchange list and recipe booklet with local recipes and spices helped in the initiation of modified Atkins diet with the flexibility of meal choices and ease of administration,” said coinvestigator Manjari Tripathi, MD, DM, department of neurology, All India Institute of Medical Science, New Delhi.

“As items were everyday household ingredients in proportion to the requirement of the modified Atkins diet, this diet is possible in low-income countries also,” Dr. Tripathi added.

The findings were published online in the journal Neurology.
 

Low carbs, high benefit

The modified Atkins diet includes around 65% fat, 25% protein, and 10% carbohydrates. Unlike a traditional ketogenic diet, the modified Atkins diet includes no restrictions on protein, calories, or fluids.

Researchers have long known that ketogenic and Atkins diets are associated with reduced seizure activity in adolescents with epilepsy. But previous studies were small, and many were retrospective analyses.

The current investigators enrolled 160 patients (80 adults, 80 adolescents) aged 10-55 years whose epilepsy was not controlled despite using at least three antiseizure medications at maximum tolerated doses.

The intervention group received training in the modified Atkins diet and were given a food exchange list, sample menu, and recipe booklet. Carbohydrate intake was restricted to 20 grams per day.

Participants took supplemental multivitamins and minerals, kept a food diary, logged seizure activity, and measured urine ketone levels three times a day. They also received weekly check-up phone calls to ensure diet adherence.

The control group received a normal diet with no carbohydrate restrictions. All participants continued their prescribed antiseizure therapy throughout the trial.
 

Primary outcome met

The primary study outcome was a reduction in seizures of more than 50%. At 6 months, 26.2% of the intervention group had reached that goal, compared with just 2.5% of the control group (P < .001).

When the median number of seizures in the modified Atkins diet group was analyzed, the frequency dropped in the intervention group from 37.5 per month at baseline to 27.5 per month after 3 months of the modified Atkins diet and to 21.5 per month after 6 months.

Adding the modified Atkins diet had a larger effect on seizure activity in adults than in adolescents. At the end of 6 months, 36% of adolescents on the modified Atkins diet had more than a 50% reduction in seizures, while 57.1% of adults on the diet reached that level.

Quality-of-life scores were also higher in the intervention group.

By the end of the trial, 5% of patients on the modified Atkins diet had no seizure activity at all versus none of the control group. In fact, the median number of seizures increased in the control group during the study.

The mean morning and evening levels of urine ketosis in the intervention group were 58.3 ± 8.0 mg/dL and 62.2 ± 22.6 mg/dL, respectively, suggesting satisfactory diet adherence. There was no significant difference between groups in weight loss.

Dr. Tripathi noted that 33% of participants did not complete the study because of poor tolerance of the diet, lack of benefit, or the inability to follow up – in part due to COVID-19. However, she said tolerance of the modified Atkins diet was better than what has been reported with the ketogenic diet.

“Though the exact mechanism by which such a diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influences the dynamics of the major inhibitory and excitatory neurotransmitter systems in the brain,” Dr. Tripathi said.
 

Benefits outweigh cost

Commenting on the research findings, Mackenzie Cervenka, MD, professor of neurology and director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore, noted that the study is the first randomized controlled trial of this size to demonstrate a benefit from adding the modified Atkins diet to standard antiseizure therapy in treatment-resistant epilepsy.

“Importantly, the study also showed improvement in quality of life and behavior over standard-of-care therapies without significant adverse effects,” said Dr. Cervenka, who was not part of the research.

The investigators noted that the flexibility of the modified Atkins diet allows more variation in menu options and a greater intake of protein, making it easier to follow than a traditional ketogenic diet.

One area of debate, however, is whether these diets are manageable for individuals with low income. Poultry, meat, and fish, all of which are staples of a modified Atkins diet, can be more expensive than other high-carb options such as pasta and rice.

“While some of the foods such as protein sources that patients purchase when they are on a ketogenic diet therapy can be more expensive, if you take into account the cost of antiseizure medications and other antiseizure treatments, hospital visits, and missed work related to seizures, et cetera, the overall financial benefits of seizure reduction with incorporating a ketogenic diet therapy may outweigh these costs,” Dr. Cervenka said.

“There are also low-cost foods that can be used since there is a great deal of flexibility with a modified Atkins diet,” she added.

The study was funded by the Centre of Excellence for Epilepsy, which is funded by the Department of Biotechnology, Government of India. Dr. Tripathi and Dr. Cervenka report no relevant financial relationships.

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

The highly anticipated Alzheimer’s drug lecanemab was granted accelerated approval status on Jan. 6 by the FDA, offering hope where there has been little for patients and their families affected by the devastating disease.

More than 6 million people in the United States live with Alzheimer’s.

It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.

But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”

Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.

So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
 

What does the FDA action mean?

The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.

The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.

With the FDA approval in hand, doctors can now prescribe the medication.

Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.

“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”

The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
 

Potential benefit?

Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.

Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
 

Concerns about side effects

The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.

Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.

Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.

“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.

The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.

“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.

Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”

The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
 

How much will it cost?

Eisai says that lecanemab will cost $26,500 a year.

In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.

An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
 

Will Medicare cover it?

The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.

That means people would have to pay thousands out of pocket at first to get it.

The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.

On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.

CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”

“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
 

Who benefits most from this drug?

Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.

Who makes lecanemab?  

Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.

What’s the Alzheimer’s Association’s view?

The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.

It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”

“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
 

Are there alternatives?

The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.

Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.

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

The highly anticipated Alzheimer’s drug lecanemab was granted accelerated approval status on Jan. 6 by the FDA, offering hope where there has been little for patients and their families affected by the devastating disease.

More than 6 million people in the United States live with Alzheimer’s.

It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.

But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”

Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.

So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
 

What does the FDA action mean?

The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.

The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.

With the FDA approval in hand, doctors can now prescribe the medication.

Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.

“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”

The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
 

Potential benefit?

Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.

Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
 

Concerns about side effects

The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.

Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.

Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.

“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.

The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.

“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.

Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”

The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
 

How much will it cost?

Eisai says that lecanemab will cost $26,500 a year.

In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.

An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
 

Will Medicare cover it?

The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.

That means people would have to pay thousands out of pocket at first to get it.

The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.

On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.

CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”

“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
 

Who benefits most from this drug?

Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.

Who makes lecanemab?  

Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.

What’s the Alzheimer’s Association’s view?

The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.

It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”

“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
 

Are there alternatives?

The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.

Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.

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

The highly anticipated Alzheimer’s drug lecanemab was granted accelerated approval status on Jan. 6 by the FDA, offering hope where there has been little for patients and their families affected by the devastating disease.

More than 6 million people in the United States live with Alzheimer’s.

It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.

But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”

Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.

So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
 

What does the FDA action mean?

The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.

The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.

With the FDA approval in hand, doctors can now prescribe the medication.

Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.

“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”

The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
 

Potential benefit?

Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.

Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
 

Concerns about side effects

The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.

Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.

Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.

“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.

The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.

“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.

Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”

The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
 

How much will it cost?

Eisai says that lecanemab will cost $26,500 a year.

In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.

An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
 

Will Medicare cover it?

The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.

That means people would have to pay thousands out of pocket at first to get it.

The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.

On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.

CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”

“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
 

Who benefits most from this drug?

Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.

Who makes lecanemab?  

Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.

What’s the Alzheimer’s Association’s view?

The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.

It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”

“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
 

Are there alternatives?

The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.

Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.

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

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.