Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.

The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.

Overall, the “OCM led to the reduced use of some high-cost supportive care medications, suggesting more value-conscious care,” study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.

The study was published online Feb. 25 in the Journal of Clinical Oncology.

Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.

The results have been decidedly mixed.

As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.

Other studies, however, have highlighted more positive results.

One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.

In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.

More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.

The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.

There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).

For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.

The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.

“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”

The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.

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

The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.

The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.

Overall, the “OCM led to the reduced use of some high-cost supportive care medications, suggesting more value-conscious care,” study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.

The study was published online Feb. 25 in the Journal of Clinical Oncology.

Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.

The results have been decidedly mixed.

As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.

Other studies, however, have highlighted more positive results.

One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.

In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.

More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.

The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.

There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).

For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.

The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.

“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”

The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.

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

The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.

The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.

Overall, the “OCM led to the reduced use of some high-cost supportive care medications, suggesting more value-conscious care,” study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.

The study was published online Feb. 25 in the Journal of Clinical Oncology.

Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.

The results have been decidedly mixed.

As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.

Other studies, however, have highlighted more positive results.

One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.

In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.

More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.

The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.

There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).

For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.

The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.

“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”

The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.

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

I was taught to think clinically first and legally second. There are moments when following every regulation is clearly detrimental to the well-being of both the patient and the medical community at large, and these challenges have been highlighted by issues with telemental health during the pandemic.

A friend emailed me with a problem: He has a son who is a traveling nurse and is currently in psychotherapy. The therapist has, in accordance with licensing requirements, told his son that she can not see him when assignments take him to any state where she is not licensed. The patient needs to physically be in the same state where the clinician holds a license, technically for every appointment. The nursing assignments last for 3 months and he will be going to a variety of states. Does he really need to get a new therapist every 90 days?

The logistics seem mind-boggling in a time when there is a shortage of mental health professionals, and there are often long wait lists to get care. And even if it was all easy, I’ll point out that working with a therapist is a bit different then going to an urgent care center to have sutures removed or to obtain antibiotics for strep throat: The relationship is not easily interchangeable, and I know of no one who would think it clinically optimal for anyone to change psychotherapists every 3 months. The traveling nurse does not just need to find a “provider” in each state, he needs to find one he is comfortable with and he will have to spend several sessions relaying his history and forming a new therapeutic alliance. And given the ambiguities of psychotherapy, he would optimally see therapists who do not make conflicting interpretations or recommendations. Mind-boggling. And while none of us are irreplaceable, it feels heartless to tell someone who is traveling to provide medical care to others during a pandemic that they can’t have mental health care when our technology would allow for it.

In the “old days” it was simpler: Patients came to the office and both the patient and the clinician were physically located in the same state, even if the patient resided in another state and commuted hours to the appointment. Telemental health was done in select rural areas or in military settings, and most physicians did not consider the option for video visits, much less full video treatment. For the average practitioner, issues of location were not relevant. The exception was for college students who might reside in one state and see a psychiatrist or therapist in another, but typically everyone was comfortable taking a break from therapy when the patient could not meet with the therapist in person. If psychiatrists were having phone or video sessions with out-of-state patients on an occasional basis, it may have been because there was less scrutiny and it was less obvious that this was not permitted.

When the pandemic forced treatment to go online, the issues changed. At the beginning, issues related to state licensing were waived. Now each state has a different requirement with regard to out-of-state physicians; some allow their residents to be seen, while others require the physician to get licensed in their state and the process may or may not be costly or arduous for the provider. The regulations change frequently, and can be quite confusing to follow. Since psychiatry is a shortage field, many psychiatrists are not looking to have more patients from other states and are not motivated to apply for extra licenses.

Life as a practicing psychiatrist has been a moving target: I reopened my practice for some in-person visits for vaccinated patients in June 2021, then closed it when the Omicron surge seemed too risky, and I’ll be reopening soon. Patients, too, have had unpredictable lives.

For the practitioner who is following the rules precisely, the issues can be sticky. It may be fine to have Zoom visits with a patient who lives across the street, but not with the elderly patient who has to drive 90 minutes across a state line, and it’s always fine to have a video session with a patient in Guam. If a patient signs on for a video visit with a doctor licensed in Maine and announces there will be a visit to a brother in Michigan, does the clinician abruptly end the session? Does he charge for the then missed appointment, and don’t we feel this is a waste of the psychiatrist’s time when appointments are limited?

If college students started with therapists in their home states when universities shut down in the spring of 2020, must they now try to get treatment in the states where their college campuses are located? What if the university has a long wait for services, there are no local psychiatrists taking on new patients, or the student feels he is making good progress with the doctor he is working with? And how do we even know for sure where our patients are located? Are we obligated to ask for a precise location at the beginning of each session? What if patients do not offer their locations, or lie about where they are?

Oddly, the issue is with the location of the patient; the doctor can be anywhere as long as the patient’s body is in a state where he or she is licensed. And it has never been a problem to send prescriptions to pharmacies in other states, though this seems to me the essence of practicing across state lines.

In the State of the Union Address on March 1, President Biden had a hefty agenda: The Russian invasion of Ukraine, a global pandemic, spiraling inflation, and for the first time in a SOTU address, our president discussed a strategy to address our National Mental Health Crisis. The fact sheet released by the White House details many long-awaited changes to increase the mental health workforce to address shortages, instituting a “988” crisis line to initiate “someone to call, someone to respond, and somewhere for every American in crisis to go.” The proposals call for a sweeping reform in providing access to services, strengthening parity, and improving community, veterans, and university services – and the Biden administration specifically addresses telemental health. “To maintain continuity of access, the Administration will work with Congress to ensure coverage of tele-behavioral health across health plans, and support appropriate delivery of telemedicine across state lines.”

This is good news, as it’s time we concentrated on allowing for access to care in a consumer-oriented way. It may let us focus on offering good clinical care and not focus on following outdated regulations. Hopefully, those who want help will be able to access it, and perhaps soon a traveling nurse will be permitted to get mental health care with continuity of treatment.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

I was taught to think clinically first and legally second. There are moments when following every regulation is clearly detrimental to the well-being of both the patient and the medical community at large, and these challenges have been highlighted by issues with telemental health during the pandemic.

A friend emailed me with a problem: He has a son who is a traveling nurse and is currently in psychotherapy. The therapist has, in accordance with licensing requirements, told his son that she can not see him when assignments take him to any state where she is not licensed. The patient needs to physically be in the same state where the clinician holds a license, technically for every appointment. The nursing assignments last for 3 months and he will be going to a variety of states. Does he really need to get a new therapist every 90 days?

The logistics seem mind-boggling in a time when there is a shortage of mental health professionals, and there are often long wait lists to get care. And even if it was all easy, I’ll point out that working with a therapist is a bit different then going to an urgent care center to have sutures removed or to obtain antibiotics for strep throat: The relationship is not easily interchangeable, and I know of no one who would think it clinically optimal for anyone to change psychotherapists every 3 months. The traveling nurse does not just need to find a “provider” in each state, he needs to find one he is comfortable with and he will have to spend several sessions relaying his history and forming a new therapeutic alliance. And given the ambiguities of psychotherapy, he would optimally see therapists who do not make conflicting interpretations or recommendations. Mind-boggling. And while none of us are irreplaceable, it feels heartless to tell someone who is traveling to provide medical care to others during a pandemic that they can’t have mental health care when our technology would allow for it.

In the “old days” it was simpler: Patients came to the office and both the patient and the clinician were physically located in the same state, even if the patient resided in another state and commuted hours to the appointment. Telemental health was done in select rural areas or in military settings, and most physicians did not consider the option for video visits, much less full video treatment. For the average practitioner, issues of location were not relevant. The exception was for college students who might reside in one state and see a psychiatrist or therapist in another, but typically everyone was comfortable taking a break from therapy when the patient could not meet with the therapist in person. If psychiatrists were having phone or video sessions with out-of-state patients on an occasional basis, it may have been because there was less scrutiny and it was less obvious that this was not permitted.

When the pandemic forced treatment to go online, the issues changed. At the beginning, issues related to state licensing were waived. Now each state has a different requirement with regard to out-of-state physicians; some allow their residents to be seen, while others require the physician to get licensed in their state and the process may or may not be costly or arduous for the provider. The regulations change frequently, and can be quite confusing to follow. Since psychiatry is a shortage field, many psychiatrists are not looking to have more patients from other states and are not motivated to apply for extra licenses.

Life as a practicing psychiatrist has been a moving target: I reopened my practice for some in-person visits for vaccinated patients in June 2021, then closed it when the Omicron surge seemed too risky, and I’ll be reopening soon. Patients, too, have had unpredictable lives.

For the practitioner who is following the rules precisely, the issues can be sticky. It may be fine to have Zoom visits with a patient who lives across the street, but not with the elderly patient who has to drive 90 minutes across a state line, and it’s always fine to have a video session with a patient in Guam. If a patient signs on for a video visit with a doctor licensed in Maine and announces there will be a visit to a brother in Michigan, does the clinician abruptly end the session? Does he charge for the then missed appointment, and don’t we feel this is a waste of the psychiatrist’s time when appointments are limited?

If college students started with therapists in their home states when universities shut down in the spring of 2020, must they now try to get treatment in the states where their college campuses are located? What if the university has a long wait for services, there are no local psychiatrists taking on new patients, or the student feels he is making good progress with the doctor he is working with? And how do we even know for sure where our patients are located? Are we obligated to ask for a precise location at the beginning of each session? What if patients do not offer their locations, or lie about where they are?

Oddly, the issue is with the location of the patient; the doctor can be anywhere as long as the patient’s body is in a state where he or she is licensed. And it has never been a problem to send prescriptions to pharmacies in other states, though this seems to me the essence of practicing across state lines.

In the State of the Union Address on March 1, President Biden had a hefty agenda: The Russian invasion of Ukraine, a global pandemic, spiraling inflation, and for the first time in a SOTU address, our president discussed a strategy to address our National Mental Health Crisis. The fact sheet released by the White House details many long-awaited changes to increase the mental health workforce to address shortages, instituting a “988” crisis line to initiate “someone to call, someone to respond, and somewhere for every American in crisis to go.” The proposals call for a sweeping reform in providing access to services, strengthening parity, and improving community, veterans, and university services – and the Biden administration specifically addresses telemental health. “To maintain continuity of access, the Administration will work with Congress to ensure coverage of tele-behavioral health across health plans, and support appropriate delivery of telemedicine across state lines.”

This is good news, as it’s time we concentrated on allowing for access to care in a consumer-oriented way. It may let us focus on offering good clinical care and not focus on following outdated regulations. Hopefully, those who want help will be able to access it, and perhaps soon a traveling nurse will be permitted to get mental health care with continuity of treatment.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

I was taught to think clinically first and legally second. There are moments when following every regulation is clearly detrimental to the well-being of both the patient and the medical community at large, and these challenges have been highlighted by issues with telemental health during the pandemic.

A friend emailed me with a problem: He has a son who is a traveling nurse and is currently in psychotherapy. The therapist has, in accordance with licensing requirements, told his son that she can not see him when assignments take him to any state where she is not licensed. The patient needs to physically be in the same state where the clinician holds a license, technically for every appointment. The nursing assignments last for 3 months and he will be going to a variety of states. Does he really need to get a new therapist every 90 days?

The logistics seem mind-boggling in a time when there is a shortage of mental health professionals, and there are often long wait lists to get care. And even if it was all easy, I’ll point out that working with a therapist is a bit different then going to an urgent care center to have sutures removed or to obtain antibiotics for strep throat: The relationship is not easily interchangeable, and I know of no one who would think it clinically optimal for anyone to change psychotherapists every 3 months. The traveling nurse does not just need to find a “provider” in each state, he needs to find one he is comfortable with and he will have to spend several sessions relaying his history and forming a new therapeutic alliance. And given the ambiguities of psychotherapy, he would optimally see therapists who do not make conflicting interpretations or recommendations. Mind-boggling. And while none of us are irreplaceable, it feels heartless to tell someone who is traveling to provide medical care to others during a pandemic that they can’t have mental health care when our technology would allow for it.

In the “old days” it was simpler: Patients came to the office and both the patient and the clinician were physically located in the same state, even if the patient resided in another state and commuted hours to the appointment. Telemental health was done in select rural areas or in military settings, and most physicians did not consider the option for video visits, much less full video treatment. For the average practitioner, issues of location were not relevant. The exception was for college students who might reside in one state and see a psychiatrist or therapist in another, but typically everyone was comfortable taking a break from therapy when the patient could not meet with the therapist in person. If psychiatrists were having phone or video sessions with out-of-state patients on an occasional basis, it may have been because there was less scrutiny and it was less obvious that this was not permitted.

When the pandemic forced treatment to go online, the issues changed. At the beginning, issues related to state licensing were waived. Now each state has a different requirement with regard to out-of-state physicians; some allow their residents to be seen, while others require the physician to get licensed in their state and the process may or may not be costly or arduous for the provider. The regulations change frequently, and can be quite confusing to follow. Since psychiatry is a shortage field, many psychiatrists are not looking to have more patients from other states and are not motivated to apply for extra licenses.

Life as a practicing psychiatrist has been a moving target: I reopened my practice for some in-person visits for vaccinated patients in June 2021, then closed it when the Omicron surge seemed too risky, and I’ll be reopening soon. Patients, too, have had unpredictable lives.

For the practitioner who is following the rules precisely, the issues can be sticky. It may be fine to have Zoom visits with a patient who lives across the street, but not with the elderly patient who has to drive 90 minutes across a state line, and it’s always fine to have a video session with a patient in Guam. If a patient signs on for a video visit with a doctor licensed in Maine and announces there will be a visit to a brother in Michigan, does the clinician abruptly end the session? Does he charge for the then missed appointment, and don’t we feel this is a waste of the psychiatrist’s time when appointments are limited?

If college students started with therapists in their home states when universities shut down in the spring of 2020, must they now try to get treatment in the states where their college campuses are located? What if the university has a long wait for services, there are no local psychiatrists taking on new patients, or the student feels he is making good progress with the doctor he is working with? And how do we even know for sure where our patients are located? Are we obligated to ask for a precise location at the beginning of each session? What if patients do not offer their locations, or lie about where they are?

Oddly, the issue is with the location of the patient; the doctor can be anywhere as long as the patient’s body is in a state where he or she is licensed. And it has never been a problem to send prescriptions to pharmacies in other states, though this seems to me the essence of practicing across state lines.

In the State of the Union Address on March 1, President Biden had a hefty agenda: The Russian invasion of Ukraine, a global pandemic, spiraling inflation, and for the first time in a SOTU address, our president discussed a strategy to address our National Mental Health Crisis. The fact sheet released by the White House details many long-awaited changes to increase the mental health workforce to address shortages, instituting a “988” crisis line to initiate “someone to call, someone to respond, and somewhere for every American in crisis to go.” The proposals call for a sweeping reform in providing access to services, strengthening parity, and improving community, veterans, and university services – and the Biden administration specifically addresses telemental health. “To maintain continuity of access, the Administration will work with Congress to ensure coverage of tele-behavioral health across health plans, and support appropriate delivery of telemedicine across state lines.”

This is good news, as it’s time we concentrated on allowing for access to care in a consumer-oriented way. It may let us focus on offering good clinical care and not focus on following outdated regulations. Hopefully, those who want help will be able to access it, and perhaps soon a traveling nurse will be permitted to get mental health care with continuity of treatment.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

Mental disorders in early life are associated with a significantly increased risk of dementia in later years.

Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.

In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.

The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.

“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.

“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.

The findings were published online Feb. 16.
 

Underappreciated risk factor

“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.

Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.

Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.

“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.

The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.

The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
 

Earlier onset

During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.

Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.

Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).

These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.

A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.

When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.

“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.

Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.

The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.

Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.

“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
 

An important risk factor

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.

He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.

“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.

The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”

Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.

However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.

Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.

Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”

The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.

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

Mental disorders in early life are associated with a significantly increased risk of dementia in later years.

Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.

In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.

The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.

“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.

“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.

The findings were published online Feb. 16.
 

Underappreciated risk factor

“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.

Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.

Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.

“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.

The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.

The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
 

Earlier onset

During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.

Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.

Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).

These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.

A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.

When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.

“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.

Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.

The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.

Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.

“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
 

An important risk factor

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.

He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.

“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.

The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”

Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.

However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.

Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.

Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”

The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.

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

Mental disorders in early life are associated with a significantly increased risk of dementia in later years.

Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.

In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.

The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.

“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.

“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.

The findings were published online Feb. 16.
 

Underappreciated risk factor

“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.

Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.

Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.

“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.

The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.

The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
 

Earlier onset

During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.

Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.

Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).

These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.

A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.

When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.

“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.

Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.

The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.

Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.

“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
 

An important risk factor

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.

He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.

“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.

The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”

Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.

However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.

Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.

Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”

The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.

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

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

A team of Canadian scientists may have discovered the first case of deer spreading the coronavirus to humans, according a new preprint study that hasn’t yet been peer-reviewed.

Typically, humans spread the virus to deer, and then deer spread it to other deer. But new evidence suggests that the virus could spill over from deer into humans. The researchers identified a COVID-19 case in someone from Ontario who had recently been in contact with deer.

“This particular case, while raising a red flag, doesn’t seem to be hugely alarming,” Finlay Maguire, PhD, one of the study authors and an epidemiologist at Dalhousie University, told CBC News.

“While we haven’t seen [transmission from deer to humans] happen directly, we sampled from the human case around the same time we sampled from the deer, and we sampled from around the same location,” he said. “There is also a plausible link by which it could have happened, in that the individual involved is known to have had considerable contact with deer.”

Dr. Maguire and colleagues have been monitoring the spread of the coronavirus among animals. They analyzed nasal swabs and lymph node samples taken from hundreds of deer that were killed by hunters in fall 2021 in southwestern and eastern Ontario. Among 298 sampled deer, 17 tested positive -- all from southwestern Ontario.

During the analysis, they found a “highly divergent” coronavirus lineage, which means a cluster of samples with many mutations. Around the same time, they found a genetically similar version in a person from the same region.

The study points to the need for better surveillance of the coronavirus, Dr. Maguire told CBC News, including in humans, animals, plants, and the broader environment. Researchers aren’t quite sure how deer contract the virus from humans, but it could happen through contaminated water, direct contact, food, farming, or other animals such as mink.

The coronavirus lineage identified in the study is different from what’s circulating among humans now, and it’s not related to the Delta or Omicron variants. The closest genetic relative came from samples taken from humans and mink in Michigan in 2020, which means the divergent lineage mutated and evolved over time.

“It’s reassuring that we found no evidence of further transmission, during a time when we were doing a lot of sampling and a lot of sequencing,” Samira Mubareka, MD, one of the study authors and a virologist at Sunnybrook Health Sciences Centre, told CBC News.

“If we continue to do this surveillance, we’ll get a much better sense of what the actual risk is,” she said.

So far, the coronavirus has been found in wild white-tailed deer in the northeastern United States and central Canadian provinces.

Other known cases of transmission from animals to humans have been identified in farmed mink and potentially hamsters, the news outlet reported. But for the most part, humans transmit the virus to animals and are most likely to catch the virus from other people.

At the same time, the Public Health Agency of Canada has issued guidance for hunters, trappers, and those who handle wild deer. People should wear gloves, goggles, and a mask when they could be exposed to respiratory tissues and fluids, especially indoors.

Coronaviruses are killed by normal cooking temperatures, the agency said, and there has been no evidence that cooked venison can spread the virus.

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

A team of Canadian scientists may have discovered the first case of deer spreading the coronavirus to humans, according a new preprint study that hasn’t yet been peer-reviewed.

Typically, humans spread the virus to deer, and then deer spread it to other deer. But new evidence suggests that the virus could spill over from deer into humans. The researchers identified a COVID-19 case in someone from Ontario who had recently been in contact with deer.

“This particular case, while raising a red flag, doesn’t seem to be hugely alarming,” Finlay Maguire, PhD, one of the study authors and an epidemiologist at Dalhousie University, told CBC News.

“While we haven’t seen [transmission from deer to humans] happen directly, we sampled from the human case around the same time we sampled from the deer, and we sampled from around the same location,” he said. “There is also a plausible link by which it could have happened, in that the individual involved is known to have had considerable contact with deer.”

Dr. Maguire and colleagues have been monitoring the spread of the coronavirus among animals. They analyzed nasal swabs and lymph node samples taken from hundreds of deer that were killed by hunters in fall 2021 in southwestern and eastern Ontario. Among 298 sampled deer, 17 tested positive -- all from southwestern Ontario.

During the analysis, they found a “highly divergent” coronavirus lineage, which means a cluster of samples with many mutations. Around the same time, they found a genetically similar version in a person from the same region.

The study points to the need for better surveillance of the coronavirus, Dr. Maguire told CBC News, including in humans, animals, plants, and the broader environment. Researchers aren’t quite sure how deer contract the virus from humans, but it could happen through contaminated water, direct contact, food, farming, or other animals such as mink.

The coronavirus lineage identified in the study is different from what’s circulating among humans now, and it’s not related to the Delta or Omicron variants. The closest genetic relative came from samples taken from humans and mink in Michigan in 2020, which means the divergent lineage mutated and evolved over time.

“It’s reassuring that we found no evidence of further transmission, during a time when we were doing a lot of sampling and a lot of sequencing,” Samira Mubareka, MD, one of the study authors and a virologist at Sunnybrook Health Sciences Centre, told CBC News.

“If we continue to do this surveillance, we’ll get a much better sense of what the actual risk is,” she said.

So far, the coronavirus has been found in wild white-tailed deer in the northeastern United States and central Canadian provinces.

Other known cases of transmission from animals to humans have been identified in farmed mink and potentially hamsters, the news outlet reported. But for the most part, humans transmit the virus to animals and are most likely to catch the virus from other people.

At the same time, the Public Health Agency of Canada has issued guidance for hunters, trappers, and those who handle wild deer. People should wear gloves, goggles, and a mask when they could be exposed to respiratory tissues and fluids, especially indoors.

Coronaviruses are killed by normal cooking temperatures, the agency said, and there has been no evidence that cooked venison can spread the virus.

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

A team of Canadian scientists may have discovered the first case of deer spreading the coronavirus to humans, according a new preprint study that hasn’t yet been peer-reviewed.

Typically, humans spread the virus to deer, and then deer spread it to other deer. But new evidence suggests that the virus could spill over from deer into humans. The researchers identified a COVID-19 case in someone from Ontario who had recently been in contact with deer.

“This particular case, while raising a red flag, doesn’t seem to be hugely alarming,” Finlay Maguire, PhD, one of the study authors and an epidemiologist at Dalhousie University, told CBC News.

“While we haven’t seen [transmission from deer to humans] happen directly, we sampled from the human case around the same time we sampled from the deer, and we sampled from around the same location,” he said. “There is also a plausible link by which it could have happened, in that the individual involved is known to have had considerable contact with deer.”

Dr. Maguire and colleagues have been monitoring the spread of the coronavirus among animals. They analyzed nasal swabs and lymph node samples taken from hundreds of deer that were killed by hunters in fall 2021 in southwestern and eastern Ontario. Among 298 sampled deer, 17 tested positive -- all from southwestern Ontario.

During the analysis, they found a “highly divergent” coronavirus lineage, which means a cluster of samples with many mutations. Around the same time, they found a genetically similar version in a person from the same region.

The study points to the need for better surveillance of the coronavirus, Dr. Maguire told CBC News, including in humans, animals, plants, and the broader environment. Researchers aren’t quite sure how deer contract the virus from humans, but it could happen through contaminated water, direct contact, food, farming, or other animals such as mink.

The coronavirus lineage identified in the study is different from what’s circulating among humans now, and it’s not related to the Delta or Omicron variants. The closest genetic relative came from samples taken from humans and mink in Michigan in 2020, which means the divergent lineage mutated and evolved over time.

“It’s reassuring that we found no evidence of further transmission, during a time when we were doing a lot of sampling and a lot of sequencing,” Samira Mubareka, MD, one of the study authors and a virologist at Sunnybrook Health Sciences Centre, told CBC News.

“If we continue to do this surveillance, we’ll get a much better sense of what the actual risk is,” she said.

So far, the coronavirus has been found in wild white-tailed deer in the northeastern United States and central Canadian provinces.

Other known cases of transmission from animals to humans have been identified in farmed mink and potentially hamsters, the news outlet reported. But for the most part, humans transmit the virus to animals and are most likely to catch the virus from other people.

At the same time, the Public Health Agency of Canada has issued guidance for hunters, trappers, and those who handle wild deer. People should wear gloves, goggles, and a mask when they could be exposed to respiratory tissues and fluids, especially indoors.

Coronaviruses are killed by normal cooking temperatures, the agency said, and there has been no evidence that cooked venison can spread the virus.

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

Four years ago, I was fully employed in a “traditional” rheumatology clinic. I met Alan, a 42-year-old gentleman who was a high school math teacher in my town. He was the first patient on my panel that day. Once I entered the examining room, Alan greeted me with: “You are the third rheumatologist who I have consulted for what everybody believes is fibromyalgia. I am paying out of pocket to see you as you are not on my insurance panel. I have researched your background, and I have high expectations of you.” He was cutting to the chase.

Alan had struggled with pain for about 1½ years. He insisted that he was very healthy before his symptoms started abruptly. In the past 2 years, his personal life had been under much stress as he was caring for a disabled child and facing an imminent divorce. While his symptoms were suggestive of an inflammatory arthritis, his workup was not. Unfortunately, the allocated time with Alan was 15 minutes – too short to cover both medical and personal struggles. Meanwhile, my nurses had to room in another two patients. I felt rushed and responsible for not letting the others wait. I asked Alan to keep a diary of his symptoms and come back in 2 weeks. A few minutes after discharging Alan, my nurse followed and asked me: “Where would you like me to add this patient, as you have no openings for 4 months ?”

“Overbook him!” I said.

This was happening almost every day. Scheduled patients, overbooked patients, tens of emails, calls to patients, and fights with insurance companies to approve tests and medications. Nearly every day I was getting home, preparing dinner, feeding my family, and going back to writing notes, as I would be financially penalized if my notes were not submitted in 24-48 hours. I had no time for my family and didn’t even think about any hobbies.

In 2 weeks, Alan came back for his visit. That day, I paid someone to take my kids to school and came to my office earlier. We had 1 hour to talk about his history. At the end of the visit, Alan said: “What kind of doctor are you? You looked into my eyes while I was talking, and you didn’t touch the computer keyboard?!” His remark was not uncommon for me. Most patients complain that physicians spend more time typing than looking at them. Maybe patients do not realize, but this is the only way that physicians get paid: writing the “proper notes” and placing the correct billing code.

Alan was diagnosed and treated successfully for seronegative rheumatoid arthritis. In 1 year, paying out of pocket to see me, he ended up spending many, many thousands of dollars. As you can imagine, I was not in control of those bills.

After 4 years in the traditional system, I decided to change something for my patients and for myself as their physician, and as a mother of three kids, a wife, a daughter, and a sister.

I decided to create a clinic where I am comfortable practicing “uncomplicated” medicine, as a friend of mine said. Today, insurance companies are restricting patients to limited panels of specialists. They dictate patients’ care, giving the false impression that they will save money. Insurance companies interfere with the physician’s medical judgment. They make algorithms to approve tests and have preferred lists of medication. They decide whether a test or a medication is appropriate for you. In addition, they don’t disclose how much they pay for your consultation, tests, and medication, and they ban the contracted parties from disclosing this information. They force patients to use their testing facilities and mailing pharmacies. Although patients and employers are the payers, they do not have access to their insurance companies’ “real” prices.

I decided that it was time to take control of my time spent with patients to make my services available when patients need me, without becoming a financial burden. I created a clinic where patients do not have copayments and will never receive a “surprise bill.” All costs are transparent to patients, including laboratory and imaging tests. Patients can talk to me on the phone, send a text, or email. A clinic where patients can talk to the physician on the phone or send a text or email? This is direct specialty care.

Is direct care a new concept? No, not at all. Is direct care the same as concierge medicine? I think it is a type of concierge service, but without the price tag.

Why?

Physicians practicing the traditional concierge medicine model here in the United States still bill patients’ insurance. In addition, to make their practice profitable, they charge a retainer fee that will allow them to keep a small patient panel. In contrast, direct care specialists do not have a contract with insurance companies.

I believe that both concierge medicine and direct care specialists offer exceptional care and better access to physicians. The difference is in costs: One is more expensive than the other. Traditional concierge medicine practices usually ask for high retainer fees in addition to copayments for visits. They do not offer any access to discounted pricing for laboratory or imaging tests. Patients continue to receive surprise bills from their insurance company.

Why don’t direct specialty care practices contract with insurance companies? Contracting with insurance companies increases a practice’s overhead costs (as more money is spent on coding and billing services and more office staff). When practice overhead is lower, the cost of patient care can be significantly lower. Patients pay a monthly membership to become a direct specialty care practice member. The membership covers the cost of visits and access to the benefits of the practice. In addition, direct care specialists do not charge copayments or send surprise bills. They can contract directly with laboratory and imaging centers and offer discounted prices. Patients with insurance are welcome to use it to cover tests, imaging, and medication. The patient has the power to choose between paying a cash price versus a “covered” service.

Most young patients, like Alan, have a high-deductible plan. A few regular blood tests might cost a patient hundreds of dollars before meeting a deductible. One MRI scan costs $4,000-$6,000. Patients who join a direct specialty care practice pay $30-$40 for regular labs and $400-$500 for an MRI.

I am now 2 years into practicing medicine as a direct care specialist. It is not a dream anymore. Yes, you may call it “concierge medicine without the price tag.” I call it “direct specialty care.” My patients and I are both accountable to one another. Together, we make a plan, and we have the time to implement it.

I am not alone. Other specialists are embracing this model. That is why we created the Direct Specialty Care Alliance, a place where physicians are welcome to network and share with others what they have learned along their journeys.

After I started my company, Alan was one of the first patients to join. He embraced my practice model and became one of the ambassadors of the direct specialty care movement. He is back to a normal life of taking care of his family, getting his wife back, and teaching math to high school kids.

Dr Girnita is the CEO and founder of RheumatologistOnCall, actively seeing patients via telemedicine in 10 U.S. states. She is an advocate for digital health and telemedicine that will empower physicians and patients to take charge of their medical care. She is a cofounder of the Direct Specialty Care Alliance. She disclosed no relevant financial relationships.

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

Four years ago, I was fully employed in a “traditional” rheumatology clinic. I met Alan, a 42-year-old gentleman who was a high school math teacher in my town. He was the first patient on my panel that day. Once I entered the examining room, Alan greeted me with: “You are the third rheumatologist who I have consulted for what everybody believes is fibromyalgia. I am paying out of pocket to see you as you are not on my insurance panel. I have researched your background, and I have high expectations of you.” He was cutting to the chase.

Alan had struggled with pain for about 1½ years. He insisted that he was very healthy before his symptoms started abruptly. In the past 2 years, his personal life had been under much stress as he was caring for a disabled child and facing an imminent divorce. While his symptoms were suggestive of an inflammatory arthritis, his workup was not. Unfortunately, the allocated time with Alan was 15 minutes – too short to cover both medical and personal struggles. Meanwhile, my nurses had to room in another two patients. I felt rushed and responsible for not letting the others wait. I asked Alan to keep a diary of his symptoms and come back in 2 weeks. A few minutes after discharging Alan, my nurse followed and asked me: “Where would you like me to add this patient, as you have no openings for 4 months ?”

“Overbook him!” I said.

This was happening almost every day. Scheduled patients, overbooked patients, tens of emails, calls to patients, and fights with insurance companies to approve tests and medications. Nearly every day I was getting home, preparing dinner, feeding my family, and going back to writing notes, as I would be financially penalized if my notes were not submitted in 24-48 hours. I had no time for my family and didn’t even think about any hobbies.

In 2 weeks, Alan came back for his visit. That day, I paid someone to take my kids to school and came to my office earlier. We had 1 hour to talk about his history. At the end of the visit, Alan said: “What kind of doctor are you? You looked into my eyes while I was talking, and you didn’t touch the computer keyboard?!” His remark was not uncommon for me. Most patients complain that physicians spend more time typing than looking at them. Maybe patients do not realize, but this is the only way that physicians get paid: writing the “proper notes” and placing the correct billing code.

Alan was diagnosed and treated successfully for seronegative rheumatoid arthritis. In 1 year, paying out of pocket to see me, he ended up spending many, many thousands of dollars. As you can imagine, I was not in control of those bills.

After 4 years in the traditional system, I decided to change something for my patients and for myself as their physician, and as a mother of three kids, a wife, a daughter, and a sister.

I decided to create a clinic where I am comfortable practicing “uncomplicated” medicine, as a friend of mine said. Today, insurance companies are restricting patients to limited panels of specialists. They dictate patients’ care, giving the false impression that they will save money. Insurance companies interfere with the physician’s medical judgment. They make algorithms to approve tests and have preferred lists of medication. They decide whether a test or a medication is appropriate for you. In addition, they don’t disclose how much they pay for your consultation, tests, and medication, and they ban the contracted parties from disclosing this information. They force patients to use their testing facilities and mailing pharmacies. Although patients and employers are the payers, they do not have access to their insurance companies’ “real” prices.

I decided that it was time to take control of my time spent with patients to make my services available when patients need me, without becoming a financial burden. I created a clinic where patients do not have copayments and will never receive a “surprise bill.” All costs are transparent to patients, including laboratory and imaging tests. Patients can talk to me on the phone, send a text, or email. A clinic where patients can talk to the physician on the phone or send a text or email? This is direct specialty care.

Is direct care a new concept? No, not at all. Is direct care the same as concierge medicine? I think it is a type of concierge service, but without the price tag.

Why?

Physicians practicing the traditional concierge medicine model here in the United States still bill patients’ insurance. In addition, to make their practice profitable, they charge a retainer fee that will allow them to keep a small patient panel. In contrast, direct care specialists do not have a contract with insurance companies.

I believe that both concierge medicine and direct care specialists offer exceptional care and better access to physicians. The difference is in costs: One is more expensive than the other. Traditional concierge medicine practices usually ask for high retainer fees in addition to copayments for visits. They do not offer any access to discounted pricing for laboratory or imaging tests. Patients continue to receive surprise bills from their insurance company.

Why don’t direct specialty care practices contract with insurance companies? Contracting with insurance companies increases a practice’s overhead costs (as more money is spent on coding and billing services and more office staff). When practice overhead is lower, the cost of patient care can be significantly lower. Patients pay a monthly membership to become a direct specialty care practice member. The membership covers the cost of visits and access to the benefits of the practice. In addition, direct care specialists do not charge copayments or send surprise bills. They can contract directly with laboratory and imaging centers and offer discounted prices. Patients with insurance are welcome to use it to cover tests, imaging, and medication. The patient has the power to choose between paying a cash price versus a “covered” service.

Most young patients, like Alan, have a high-deductible plan. A few regular blood tests might cost a patient hundreds of dollars before meeting a deductible. One MRI scan costs $4,000-$6,000. Patients who join a direct specialty care practice pay $30-$40 for regular labs and $400-$500 for an MRI.

I am now 2 years into practicing medicine as a direct care specialist. It is not a dream anymore. Yes, you may call it “concierge medicine without the price tag.” I call it “direct specialty care.” My patients and I are both accountable to one another. Together, we make a plan, and we have the time to implement it.

I am not alone. Other specialists are embracing this model. That is why we created the Direct Specialty Care Alliance, a place where physicians are welcome to network and share with others what they have learned along their journeys.

After I started my company, Alan was one of the first patients to join. He embraced my practice model and became one of the ambassadors of the direct specialty care movement. He is back to a normal life of taking care of his family, getting his wife back, and teaching math to high school kids.

Dr Girnita is the CEO and founder of RheumatologistOnCall, actively seeing patients via telemedicine in 10 U.S. states. She is an advocate for digital health and telemedicine that will empower physicians and patients to take charge of their medical care. She is a cofounder of the Direct Specialty Care Alliance. She disclosed no relevant financial relationships.

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

Four years ago, I was fully employed in a “traditional” rheumatology clinic. I met Alan, a 42-year-old gentleman who was a high school math teacher in my town. He was the first patient on my panel that day. Once I entered the examining room, Alan greeted me with: “You are the third rheumatologist who I have consulted for what everybody believes is fibromyalgia. I am paying out of pocket to see you as you are not on my insurance panel. I have researched your background, and I have high expectations of you.” He was cutting to the chase.

Alan had struggled with pain for about 1½ years. He insisted that he was very healthy before his symptoms started abruptly. In the past 2 years, his personal life had been under much stress as he was caring for a disabled child and facing an imminent divorce. While his symptoms were suggestive of an inflammatory arthritis, his workup was not. Unfortunately, the allocated time with Alan was 15 minutes – too short to cover both medical and personal struggles. Meanwhile, my nurses had to room in another two patients. I felt rushed and responsible for not letting the others wait. I asked Alan to keep a diary of his symptoms and come back in 2 weeks. A few minutes after discharging Alan, my nurse followed and asked me: “Where would you like me to add this patient, as you have no openings for 4 months ?”

“Overbook him!” I said.

This was happening almost every day. Scheduled patients, overbooked patients, tens of emails, calls to patients, and fights with insurance companies to approve tests and medications. Nearly every day I was getting home, preparing dinner, feeding my family, and going back to writing notes, as I would be financially penalized if my notes were not submitted in 24-48 hours. I had no time for my family and didn’t even think about any hobbies.

In 2 weeks, Alan came back for his visit. That day, I paid someone to take my kids to school and came to my office earlier. We had 1 hour to talk about his history. At the end of the visit, Alan said: “What kind of doctor are you? You looked into my eyes while I was talking, and you didn’t touch the computer keyboard?!” His remark was not uncommon for me. Most patients complain that physicians spend more time typing than looking at them. Maybe patients do not realize, but this is the only way that physicians get paid: writing the “proper notes” and placing the correct billing code.

Alan was diagnosed and treated successfully for seronegative rheumatoid arthritis. In 1 year, paying out of pocket to see me, he ended up spending many, many thousands of dollars. As you can imagine, I was not in control of those bills.

After 4 years in the traditional system, I decided to change something for my patients and for myself as their physician, and as a mother of three kids, a wife, a daughter, and a sister.

I decided to create a clinic where I am comfortable practicing “uncomplicated” medicine, as a friend of mine said. Today, insurance companies are restricting patients to limited panels of specialists. They dictate patients’ care, giving the false impression that they will save money. Insurance companies interfere with the physician’s medical judgment. They make algorithms to approve tests and have preferred lists of medication. They decide whether a test or a medication is appropriate for you. In addition, they don’t disclose how much they pay for your consultation, tests, and medication, and they ban the contracted parties from disclosing this information. They force patients to use their testing facilities and mailing pharmacies. Although patients and employers are the payers, they do not have access to their insurance companies’ “real” prices.

I decided that it was time to take control of my time spent with patients to make my services available when patients need me, without becoming a financial burden. I created a clinic where patients do not have copayments and will never receive a “surprise bill.” All costs are transparent to patients, including laboratory and imaging tests. Patients can talk to me on the phone, send a text, or email. A clinic where patients can talk to the physician on the phone or send a text or email? This is direct specialty care.

Is direct care a new concept? No, not at all. Is direct care the same as concierge medicine? I think it is a type of concierge service, but without the price tag.

Why?

Physicians practicing the traditional concierge medicine model here in the United States still bill patients’ insurance. In addition, to make their practice profitable, they charge a retainer fee that will allow them to keep a small patient panel. In contrast, direct care specialists do not have a contract with insurance companies.

I believe that both concierge medicine and direct care specialists offer exceptional care and better access to physicians. The difference is in costs: One is more expensive than the other. Traditional concierge medicine practices usually ask for high retainer fees in addition to copayments for visits. They do not offer any access to discounted pricing for laboratory or imaging tests. Patients continue to receive surprise bills from their insurance company.

Why don’t direct specialty care practices contract with insurance companies? Contracting with insurance companies increases a practice’s overhead costs (as more money is spent on coding and billing services and more office staff). When practice overhead is lower, the cost of patient care can be significantly lower. Patients pay a monthly membership to become a direct specialty care practice member. The membership covers the cost of visits and access to the benefits of the practice. In addition, direct care specialists do not charge copayments or send surprise bills. They can contract directly with laboratory and imaging centers and offer discounted prices. Patients with insurance are welcome to use it to cover tests, imaging, and medication. The patient has the power to choose between paying a cash price versus a “covered” service.

Most young patients, like Alan, have a high-deductible plan. A few regular blood tests might cost a patient hundreds of dollars before meeting a deductible. One MRI scan costs $4,000-$6,000. Patients who join a direct specialty care practice pay $30-$40 for regular labs and $400-$500 for an MRI.

I am now 2 years into practicing medicine as a direct care specialist. It is not a dream anymore. Yes, you may call it “concierge medicine without the price tag.” I call it “direct specialty care.” My patients and I are both accountable to one another. Together, we make a plan, and we have the time to implement it.

I am not alone. Other specialists are embracing this model. That is why we created the Direct Specialty Care Alliance, a place where physicians are welcome to network and share with others what they have learned along their journeys.

After I started my company, Alan was one of the first patients to join. He embraced my practice model and became one of the ambassadors of the direct specialty care movement. He is back to a normal life of taking care of his family, getting his wife back, and teaching math to high school kids.

Dr Girnita is the CEO and founder of RheumatologistOnCall, actively seeing patients via telemedicine in 10 U.S. states. She is an advocate for digital health and telemedicine that will empower physicians and patients to take charge of their medical care. She is a cofounder of the Direct Specialty Care Alliance. She disclosed no relevant financial relationships.

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

The European Medicines Agency’s (EMA’s) human medicines committee has recommended approval of a hepatitis B vaccine for adults.

The agency’s Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for PreHevbri on Feb. 24 for active immunization against hepatitis B virus (HBV) infection. PreHevbri (PreHevBrio in the United States and Sci-B-Vac in Israel) received approval from the Food and Drug Administration on Nov. 30, 2021. The vaccine is produced by VBI Vaccines (Delaware) Inc., based in Cambridge, Mass.

The World Health Organization estimates that more than 290 million people globally are infected with HBV. HBV is the leading cause of liver disease, and an estimated 900,000 people die every year from complications from chronic HBV infection, according to a VBI Vaccine press release. A 2019 report from the European Centre for Disease Prevention and Control found that adults in the European Union aged 35-44 had the highest rates of acute infections with HBV, and people aged 25-34 had the highest rate of chronic HBV infections. Vaccination programs are key interventions in preventing transmission of the virus, the report noted.

PreHevbri is a hepatitis B vaccine composed of three surface antigens of the hepatitis B virus. The vaccine is administered via injection in three doses on a 0-, 1-, and 6-month schedule and is indicated for use in adults aged 18 years and older.

The CHMP recommendation was based on data from a safety and immunogenicity study, which included 1,607 participants aged 18 and older, and a lot-to-lot study, which included 2,838 adults aged 18-45, according the VBI vaccine press release.

The recommendation will now be reviewed by the European Commission. If approved, PreHevbri will be the only three-antigen HBV vaccine for adults approved in the European Union.

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

The European Medicines Agency’s (EMA’s) human medicines committee has recommended approval of a hepatitis B vaccine for adults.

The agency’s Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for PreHevbri on Feb. 24 for active immunization against hepatitis B virus (HBV) infection. PreHevbri (PreHevBrio in the United States and Sci-B-Vac in Israel) received approval from the Food and Drug Administration on Nov. 30, 2021. The vaccine is produced by VBI Vaccines (Delaware) Inc., based in Cambridge, Mass.

The World Health Organization estimates that more than 290 million people globally are infected with HBV. HBV is the leading cause of liver disease, and an estimated 900,000 people die every year from complications from chronic HBV infection, according to a VBI Vaccine press release. A 2019 report from the European Centre for Disease Prevention and Control found that adults in the European Union aged 35-44 had the highest rates of acute infections with HBV, and people aged 25-34 had the highest rate of chronic HBV infections. Vaccination programs are key interventions in preventing transmission of the virus, the report noted.

PreHevbri is a hepatitis B vaccine composed of three surface antigens of the hepatitis B virus. The vaccine is administered via injection in three doses on a 0-, 1-, and 6-month schedule and is indicated for use in adults aged 18 years and older.

The CHMP recommendation was based on data from a safety and immunogenicity study, which included 1,607 participants aged 18 and older, and a lot-to-lot study, which included 2,838 adults aged 18-45, according the VBI vaccine press release.

The recommendation will now be reviewed by the European Commission. If approved, PreHevbri will be the only three-antigen HBV vaccine for adults approved in the European Union.

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

The European Medicines Agency’s (EMA’s) human medicines committee has recommended approval of a hepatitis B vaccine for adults.

The agency’s Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for PreHevbri on Feb. 24 for active immunization against hepatitis B virus (HBV) infection. PreHevbri (PreHevBrio in the United States and Sci-B-Vac in Israel) received approval from the Food and Drug Administration on Nov. 30, 2021. The vaccine is produced by VBI Vaccines (Delaware) Inc., based in Cambridge, Mass.

The World Health Organization estimates that more than 290 million people globally are infected with HBV. HBV is the leading cause of liver disease, and an estimated 900,000 people die every year from complications from chronic HBV infection, according to a VBI Vaccine press release. A 2019 report from the European Centre for Disease Prevention and Control found that adults in the European Union aged 35-44 had the highest rates of acute infections with HBV, and people aged 25-34 had the highest rate of chronic HBV infections. Vaccination programs are key interventions in preventing transmission of the virus, the report noted.

PreHevbri is a hepatitis B vaccine composed of three surface antigens of the hepatitis B virus. The vaccine is administered via injection in three doses on a 0-, 1-, and 6-month schedule and is indicated for use in adults aged 18 years and older.

The CHMP recommendation was based on data from a safety and immunogenicity study, which included 1,607 participants aged 18 and older, and a lot-to-lot study, which included 2,838 adults aged 18-45, according the VBI vaccine press release.

The recommendation will now be reviewed by the European Commission. If approved, PreHevbri will be the only three-antigen HBV vaccine for adults approved in the European Union.

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

WEST PALM BEACH, FLA. – The presence of paramagnetic rim lesions (PRLs) on MRI may help in the diagnosis of multiple sclerosis (MS), as well as in predicting more severe disease course, new research suggests.

Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.

Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.

“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.

The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
 

Sign of aggressive disease?

Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.

In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.

At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).

At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.

Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.

The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).

After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).

Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).

“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.

“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.

Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
 

Diagnostic value

The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).

Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.

Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.

Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.

“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
 

Promising data

During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.

“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.

“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.

Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”

Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”

Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.

“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.

During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.

Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.

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

WEST PALM BEACH, FLA. – The presence of paramagnetic rim lesions (PRLs) on MRI may help in the diagnosis of multiple sclerosis (MS), as well as in predicting more severe disease course, new research suggests.

Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.

Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.

“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.

The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
 

Sign of aggressive disease?

Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.

In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.

At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).

At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.

Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.

The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).

After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).

Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).

“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.

“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.

Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
 

Diagnostic value

The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).

Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.

Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.

Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.

“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
 

Promising data

During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.

“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.

“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.

Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”

Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”

Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.

“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.

During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.

Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.

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

WEST PALM BEACH, FLA. – The presence of paramagnetic rim lesions (PRLs) on MRI may help in the diagnosis of multiple sclerosis (MS), as well as in predicting more severe disease course, new research suggests.

Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.

Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.

“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.

The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
 

Sign of aggressive disease?

Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.

In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.

At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).

At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.

Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.

The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).

After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).

Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).

“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.

“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.

Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
 

Diagnostic value

The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).

Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.

Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.

Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.

“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
 

Promising data

During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.

“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.

“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.

Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”

Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”

Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.

“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.

During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.

Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.

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

WEST PALM BEACH, FLA. – Spinal cord atrophy, as detected on calibrated brain MRI scans, significantly correlates with silent progression of multiple sclerosis (MS) to progressive MS, new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.

“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.

“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.

Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Relatively new concept

Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.

However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.

“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).

To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.

They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.

To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.

Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
 

‘Strongest predictor’

The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).

Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).

“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.

Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.

Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).

“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
 

Standard of care?

While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.

Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.

“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
 

Treatment implications

Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.

“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.

Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.

“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.

Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.

He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.

“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.

Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.

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

WEST PALM BEACH, FLA. – Spinal cord atrophy, as detected on calibrated brain MRI scans, significantly correlates with silent progression of multiple sclerosis (MS) to progressive MS, new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.

“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.

“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.

Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Relatively new concept

Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.

However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.

“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).

To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.

They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.

To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.

Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
 

‘Strongest predictor’

The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).

Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).

“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.

Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.

Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).

“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
 

Standard of care?

While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.

Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.

“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
 

Treatment implications

Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.

“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.

Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.

“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.

Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.

He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.

“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.

Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.

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

WEST PALM BEACH, FLA. – Spinal cord atrophy, as detected on calibrated brain MRI scans, significantly correlates with silent progression of multiple sclerosis (MS) to progressive MS, new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.

“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.

“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.

Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Relatively new concept

Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.

However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.

“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).

To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.

They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.

To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.

Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
 

‘Strongest predictor’

The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).

Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).

“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.

Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.

Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).

“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
 

Standard of care?

While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.

Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.

“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
 

Treatment implications

Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.

“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.

Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.

“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.

Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.

He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.

“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.

Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.

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