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TNF inhibitors linked to inflammatory CNS events
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
FDA clears first brain stimulation device to help smokers quit
The Food and Drug Administration has granted marketing approval for the BrainsWay deep transcranial magnetic stimulation (TMS) system to help adult smokers kick tobacco.
in a press release.
As previously reported, the system has already been approved by the FDA as a treatment for patients suffering from obsessive-compulsive disorder and major depressive disorder.
The BrainsWay deep TMS system with H4-coil is designed to target addiction-related brain circuits.
It was evaluated as an aid to short-term smoking cessation in a prospective, double-blind, randomized, sham-controlled, multicenter study that involved 262 adults who had a history of smoking an average of more than 26 years and had attempted to quit multiple times but failed.
Active and sham treatments were performed daily 5 days a week for 3 weeks, followed by an additional three sessions once weekly for 3 weeks, for a total of 18 sessions over 6 weeks.
In the full intention-to-treat population (all 262 participants), the 4-week continuous quit rate (CQR, the primary endpoint) was higher in the active deep TMS group than in the sham TMS group (17.1% vs. 7.9%; P = .0238).
Among participants who completed the study, that is, those who underwent treatment for 4 weeks, who kept daily records, and for whom confirmatory urine samples were available, the CQR was 28.4% in the active deep TMS group, compared with 11.7% in the sham treatment group (P = .0063).
The average number of cigarettes smoked per day, as determined on the basis of daily records (secondary endpoint), was statistically significantly lower in the active deep TMS group, compared with the sham treatment group (P = .0311).
No patient suffered a seizure. The most common adverse event was headache, for which there was no statistical difference between the active and sham treatment groups. Other side effects included application site discomfort, back pain, muscle twitching, and discomfort.
“This FDA clearance represents a significant milestone for BrainsWay and our deep TMS platform technology,” Christopher von Jako, PhD, president and CEO of the company, said in the release.
“While other therapies are currently available, a substantial medical need continues to exist for treatments that can increase the continuous quit rate among smokers,” Dr. von Jako noted.
“Based on the compelling data from our large, randomized pivotal study of 262 subjects, we are confident that our deep TMS technology can play an important role in treating cigarette smokers who seek to quit,” he added.
The company plans a “controlled” U.S. market release of the system for this indication early next year.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has granted marketing approval for the BrainsWay deep transcranial magnetic stimulation (TMS) system to help adult smokers kick tobacco.
in a press release.
As previously reported, the system has already been approved by the FDA as a treatment for patients suffering from obsessive-compulsive disorder and major depressive disorder.
The BrainsWay deep TMS system with H4-coil is designed to target addiction-related brain circuits.
It was evaluated as an aid to short-term smoking cessation in a prospective, double-blind, randomized, sham-controlled, multicenter study that involved 262 adults who had a history of smoking an average of more than 26 years and had attempted to quit multiple times but failed.
Active and sham treatments were performed daily 5 days a week for 3 weeks, followed by an additional three sessions once weekly for 3 weeks, for a total of 18 sessions over 6 weeks.
In the full intention-to-treat population (all 262 participants), the 4-week continuous quit rate (CQR, the primary endpoint) was higher in the active deep TMS group than in the sham TMS group (17.1% vs. 7.9%; P = .0238).
Among participants who completed the study, that is, those who underwent treatment for 4 weeks, who kept daily records, and for whom confirmatory urine samples were available, the CQR was 28.4% in the active deep TMS group, compared with 11.7% in the sham treatment group (P = .0063).
The average number of cigarettes smoked per day, as determined on the basis of daily records (secondary endpoint), was statistically significantly lower in the active deep TMS group, compared with the sham treatment group (P = .0311).
No patient suffered a seizure. The most common adverse event was headache, for which there was no statistical difference between the active and sham treatment groups. Other side effects included application site discomfort, back pain, muscle twitching, and discomfort.
“This FDA clearance represents a significant milestone for BrainsWay and our deep TMS platform technology,” Christopher von Jako, PhD, president and CEO of the company, said in the release.
“While other therapies are currently available, a substantial medical need continues to exist for treatments that can increase the continuous quit rate among smokers,” Dr. von Jako noted.
“Based on the compelling data from our large, randomized pivotal study of 262 subjects, we are confident that our deep TMS technology can play an important role in treating cigarette smokers who seek to quit,” he added.
The company plans a “controlled” U.S. market release of the system for this indication early next year.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has granted marketing approval for the BrainsWay deep transcranial magnetic stimulation (TMS) system to help adult smokers kick tobacco.
in a press release.
As previously reported, the system has already been approved by the FDA as a treatment for patients suffering from obsessive-compulsive disorder and major depressive disorder.
The BrainsWay deep TMS system with H4-coil is designed to target addiction-related brain circuits.
It was evaluated as an aid to short-term smoking cessation in a prospective, double-blind, randomized, sham-controlled, multicenter study that involved 262 adults who had a history of smoking an average of more than 26 years and had attempted to quit multiple times but failed.
Active and sham treatments were performed daily 5 days a week for 3 weeks, followed by an additional three sessions once weekly for 3 weeks, for a total of 18 sessions over 6 weeks.
In the full intention-to-treat population (all 262 participants), the 4-week continuous quit rate (CQR, the primary endpoint) was higher in the active deep TMS group than in the sham TMS group (17.1% vs. 7.9%; P = .0238).
Among participants who completed the study, that is, those who underwent treatment for 4 weeks, who kept daily records, and for whom confirmatory urine samples were available, the CQR was 28.4% in the active deep TMS group, compared with 11.7% in the sham treatment group (P = .0063).
The average number of cigarettes smoked per day, as determined on the basis of daily records (secondary endpoint), was statistically significantly lower in the active deep TMS group, compared with the sham treatment group (P = .0311).
No patient suffered a seizure. The most common adverse event was headache, for which there was no statistical difference between the active and sham treatment groups. Other side effects included application site discomfort, back pain, muscle twitching, and discomfort.
“This FDA clearance represents a significant milestone for BrainsWay and our deep TMS platform technology,” Christopher von Jako, PhD, president and CEO of the company, said in the release.
“While other therapies are currently available, a substantial medical need continues to exist for treatments that can increase the continuous quit rate among smokers,” Dr. von Jako noted.
“Based on the compelling data from our large, randomized pivotal study of 262 subjects, we are confident that our deep TMS technology can play an important role in treating cigarette smokers who seek to quit,” he added.
The company plans a “controlled” U.S. market release of the system for this indication early next year.
A version of this article originally appeared on Medscape.com.
Clinical pearls for administering cognitive exams during the pandemic
Patients have often been labeled as “poor historians” if they are not able to recollect their own medical history, whether through illness or difficulties in communication. But Fred Ovsiew, MD, speaking at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sees that label as an excuse on the part of the clinician.
“I strongly advise you to drop that phrase from your vocabulary if you do use it, because the patient is not the historian. The doctor, the clinician is the historian,” Dr. Ovsiew said at the meeting, presented by Global Academy for Medical Education. “It is the clinician’s job to put the story together using the account by the patient as one source, but [also] interviewing a collateral informant and/or reviewing records, which is necessary in almost every case of a neuropsychiatric illness.”
Rather, clinicians taking history at the bedside should focus on why the patients cannot give a narrative account of their illness. Patients can have narrative incapacity on a psychogenic basis, such as in patients with conversion or somatoform disorder, he explained. “I think this is a result of the narrative incapacity that develops in people who have had trauma or adverse experiences in childhood and insecure attachment. This is shown on the adult attachment interview as a disorganized account of their childhoods.”
Other patients might not be able to recount their medical history because they are amnestic, which leaves their account vague because of a lack of access to information. “It may be frozen in time in the sense that, up to a certain point in their life, they can recount the history,” Dr. Ovsiew said. “But in recent years, their account becomes vague.”
Patients with right hemisphere lesions might not know that their account has incongruity and is implausible, while patients with dorsolateral prefrontal lesions might be aspontaneous, use few words to describe their situation, and have poor insight. Those with ventromedial prefrontal lesions can be impulsive and have poor insight, not considering alternative possibilities, Dr. Ovsiew noted.
Asking open-ended questions of the patient is the first step to identifying any potential narrative incapacity, followed by a detailed medical history by the clinician. When taking a medical history, try avoiding what Dr. Ovsiew calls the “anything like that?” problem, where a clinician asks a question about a cluster of symptoms that would make sense to a doctor, but not a patient. For example, a doctor might ask whether a patient is experiencing “chest pain or leg swelling – anything like that?” because he or she knows what those symptoms have in common, but the patient might not know the relationship between those symptoms. “You can’t count on the patient to tell you all the relevant information,” he said. “You have to know what to ask about.”
“Patients with brain disease have subtle personality changes, sometimes more obvious personality changes. These need to be inquired about,” Dr. Ovsiew said. “The patient with apathy has reduced negative as well as positive emotions. The patient with depression has reduced positive emotions, but often tells you very clearly about the negative emotions of sadness, guilt. The patient with depression has diurnal variation in mood, a very telling symptom, especially when it’s disclosed spontaneously,” Dr. Ovsiew explained. “The point is, you need to know to ask about it.”
When taking a sleep history, clinicians should be aware of sleep disturbances apart from insomnia and early waking. REM sleep behavior disorder is a condition that should be inquired about. Obstructive sleep apnea is a condition that might not be immediately apparent to the patient, but a bed partner can identify whether a patient has problems breathing throughout the night.
“This is an important condition to uncover for the neuropsychiatrist because it contributes to treatment resistance and depression, and it contributes to cognitive impairment,” Dr. Ovsiew said. “These patients commonly have mild difficulties with attention and concentration.”
Always ask about head injury in every history, which can be relevant to later onset depression, PTSD, and cognitive impairment. Every head injury follows a trajectory of retrograde amnesia and altered state of consciousness (including coma), followed by a period of posttraumatic amnesia. Duration of these states can be used to assess the severity of brain injury, but the 15-point Glasgow Coma Scale is another way to assess injury severity, Dr. Ovsiew explained.
However, the two do not always overlap, he noted. “Someone may have a Glasgow Coma Scale score that is 9-12, predicting moderate brain injury, but they may have a short duration of amnesia. These don’t always follow the same path. There are many different ways of classifying how severe the brain injury is.”
Keep probes brief, straightforward
Cognitive exams of patients with suspected psychiatric disorders should be simple, easy to administer and focused on a single domain of cognition. “Probes should be brief. They should not require specialized equipment. The Purdue Pegboard Test might be a great neuropsychological instrument, but very few of us carry a pegboard around in our medical bags,” Dr. Ovsiew said.
The probe administered should also be accessible to the patient. The serial sevens clinical test, where a patient is asked to repeatedly subtract 7 from 100, is only effective at testing concentration if the patient is capable of completing the test. “There are going to be patients who can’t do the task, but it’s not because of concentration failure, it’s because of subtraction failure,” he said.
When assessing attention, effective tasks include having the patient perform the digit span test forward and backward, count backward from 20 to 1, listing the months of the year in reverse, and performing the Mental Alternation Test. However, Dr. Ovsiew explained there may be some barriers for patients in completing these tasks. “The person may be aphasic and not know the alphabet. The person may have English as a second language and not be skilled at giving the alphabet in English. In some cases, you may want to check and not assume that the patient can count and does know the alphabet.”
In assessing language, listen for aphasic abnormalities. “The patient, of course, is speaking throughout the interview, but you need to take a moment to listen for prosody, to listen to rate of speech, to listen for paraphasic errors or word-finding problems,” Dr. Ovsiew said. Any abnormalities should be probed further through confrontation naming tasks, which can be done in person and with some success through video, but not by phone. Naming to definition (“What do you call the part of a shirt that covers the arm?”) is one way of administering the test over the phone.
Visuospatial function can be assessed by clock drawing but also carries problems. Patients who do not plan their clock before beginning to draw, for example, may have an executive function problem instead of a visuospatial problem, Dr. Ovsiew noted. Patients in whom a clinician suspects hemineglect should be given a visual search task or line by section task. “I like doing clock drawing. It’s a nice screening test. It’s becoming, I think, less useful as people count on digital clocks and have trouble even imagining what an analog clock looks like.”
An approach that is better suited to in-person assessment, but also works by video, is the Poppelreuter figure visual perceptual function test, which is a prompt for the patient that involves common household items overlaying one another “in atypical positions and atypical configurations” where the patient is instructed to describe the items they see on the card. Another approach that works over video is the interlocking finger test, where the patient is asked to copy the hand positions made by the clinician.
Dr. Ovsiew admitted that visuospatial function is nearly impossible to assess over the phone. Asking topographical questions (“If you’re driving from Chicago to Los Angeles, is the Pacific Ocean in front of you, behind you, to your left, or to your right?”) may help judge visuospatial function, but this relies on the patient having the topographic knowledge to answer the questions. Some patients who are topographically disoriented can’t do them at all,” Dr. Ovsiew said.
Bedside neuropsychiatry assesses encoding of a memory, its retention and its retrieval as well as verbal and visual cues. Each one of these aspects of memory can be impaired on its own and should be explored separately, Dr. Ovsiew explained. “Neuropsychiatric clinicians have a rough-and-ready, seat-of-the-pants way of approaching this that wouldn’t pass muster if you’re a psychologist, but is the best we can do at the bedside.”
To test retrieval and retention, the Three Words–Three Shapes test works well in person, with some difficulty by video, and is not possible to administer over the phone. In lieu of that test, giving the patient a simple word list and asking them to repeat the list in order. Using the word list, “these different stages of memory function can be parsed out pretty well at the bedside or chairside, and even by the phone. Figuring out where the memory failure is diagnostically important,” Dr. Ovsiew said.
Executive function, which involves activation, planning, sequencing, maintaining, self-monitoring, and flexible employment of action and attention, is “complicated to evaluate because there are multiple aspects of executive function, multiple deficits that can be seen with executive dysfunction, and they don’t all correlate with each other.”
Within executive function evaluation, the Mental Alternation Test can assess working memory, motor sequencing can be assessed through the ring/fist, fist/edge/palm, alternating fist, and rampart tests. The Go/No-Go test can be used to assess response inhibition. For effortful retrieval evaluation, spontaneous word-list generation – such as thinking of all the items one can buy at a supermarket– can test category fluency, while a task to name all the words starting with a certain letter can assess letter stimulus.
Executive function “is of crucial importance in the neuropsychiatric evaluation because it’s strongly correlated with how well the person functions outside the office,” Dr. Ovsiew said.
Global Academy and this news organization are owned by the same parent company. Dr. Ovsiew reported relationships with Wolters Kluwer Health in the form of consulting, receiving royalty payments, and related activities.
Patients have often been labeled as “poor historians” if they are not able to recollect their own medical history, whether through illness or difficulties in communication. But Fred Ovsiew, MD, speaking at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sees that label as an excuse on the part of the clinician.
“I strongly advise you to drop that phrase from your vocabulary if you do use it, because the patient is not the historian. The doctor, the clinician is the historian,” Dr. Ovsiew said at the meeting, presented by Global Academy for Medical Education. “It is the clinician’s job to put the story together using the account by the patient as one source, but [also] interviewing a collateral informant and/or reviewing records, which is necessary in almost every case of a neuropsychiatric illness.”
Rather, clinicians taking history at the bedside should focus on why the patients cannot give a narrative account of their illness. Patients can have narrative incapacity on a psychogenic basis, such as in patients with conversion or somatoform disorder, he explained. “I think this is a result of the narrative incapacity that develops in people who have had trauma or adverse experiences in childhood and insecure attachment. This is shown on the adult attachment interview as a disorganized account of their childhoods.”
Other patients might not be able to recount their medical history because they are amnestic, which leaves their account vague because of a lack of access to information. “It may be frozen in time in the sense that, up to a certain point in their life, they can recount the history,” Dr. Ovsiew said. “But in recent years, their account becomes vague.”
Patients with right hemisphere lesions might not know that their account has incongruity and is implausible, while patients with dorsolateral prefrontal lesions might be aspontaneous, use few words to describe their situation, and have poor insight. Those with ventromedial prefrontal lesions can be impulsive and have poor insight, not considering alternative possibilities, Dr. Ovsiew noted.
Asking open-ended questions of the patient is the first step to identifying any potential narrative incapacity, followed by a detailed medical history by the clinician. When taking a medical history, try avoiding what Dr. Ovsiew calls the “anything like that?” problem, where a clinician asks a question about a cluster of symptoms that would make sense to a doctor, but not a patient. For example, a doctor might ask whether a patient is experiencing “chest pain or leg swelling – anything like that?” because he or she knows what those symptoms have in common, but the patient might not know the relationship between those symptoms. “You can’t count on the patient to tell you all the relevant information,” he said. “You have to know what to ask about.”
“Patients with brain disease have subtle personality changes, sometimes more obvious personality changes. These need to be inquired about,” Dr. Ovsiew said. “The patient with apathy has reduced negative as well as positive emotions. The patient with depression has reduced positive emotions, but often tells you very clearly about the negative emotions of sadness, guilt. The patient with depression has diurnal variation in mood, a very telling symptom, especially when it’s disclosed spontaneously,” Dr. Ovsiew explained. “The point is, you need to know to ask about it.”
When taking a sleep history, clinicians should be aware of sleep disturbances apart from insomnia and early waking. REM sleep behavior disorder is a condition that should be inquired about. Obstructive sleep apnea is a condition that might not be immediately apparent to the patient, but a bed partner can identify whether a patient has problems breathing throughout the night.
“This is an important condition to uncover for the neuropsychiatrist because it contributes to treatment resistance and depression, and it contributes to cognitive impairment,” Dr. Ovsiew said. “These patients commonly have mild difficulties with attention and concentration.”
Always ask about head injury in every history, which can be relevant to later onset depression, PTSD, and cognitive impairment. Every head injury follows a trajectory of retrograde amnesia and altered state of consciousness (including coma), followed by a period of posttraumatic amnesia. Duration of these states can be used to assess the severity of brain injury, but the 15-point Glasgow Coma Scale is another way to assess injury severity, Dr. Ovsiew explained.
However, the two do not always overlap, he noted. “Someone may have a Glasgow Coma Scale score that is 9-12, predicting moderate brain injury, but they may have a short duration of amnesia. These don’t always follow the same path. There are many different ways of classifying how severe the brain injury is.”
Keep probes brief, straightforward
Cognitive exams of patients with suspected psychiatric disorders should be simple, easy to administer and focused on a single domain of cognition. “Probes should be brief. They should not require specialized equipment. The Purdue Pegboard Test might be a great neuropsychological instrument, but very few of us carry a pegboard around in our medical bags,” Dr. Ovsiew said.
The probe administered should also be accessible to the patient. The serial sevens clinical test, where a patient is asked to repeatedly subtract 7 from 100, is only effective at testing concentration if the patient is capable of completing the test. “There are going to be patients who can’t do the task, but it’s not because of concentration failure, it’s because of subtraction failure,” he said.
When assessing attention, effective tasks include having the patient perform the digit span test forward and backward, count backward from 20 to 1, listing the months of the year in reverse, and performing the Mental Alternation Test. However, Dr. Ovsiew explained there may be some barriers for patients in completing these tasks. “The person may be aphasic and not know the alphabet. The person may have English as a second language and not be skilled at giving the alphabet in English. In some cases, you may want to check and not assume that the patient can count and does know the alphabet.”
In assessing language, listen for aphasic abnormalities. “The patient, of course, is speaking throughout the interview, but you need to take a moment to listen for prosody, to listen to rate of speech, to listen for paraphasic errors or word-finding problems,” Dr. Ovsiew said. Any abnormalities should be probed further through confrontation naming tasks, which can be done in person and with some success through video, but not by phone. Naming to definition (“What do you call the part of a shirt that covers the arm?”) is one way of administering the test over the phone.
Visuospatial function can be assessed by clock drawing but also carries problems. Patients who do not plan their clock before beginning to draw, for example, may have an executive function problem instead of a visuospatial problem, Dr. Ovsiew noted. Patients in whom a clinician suspects hemineglect should be given a visual search task or line by section task. “I like doing clock drawing. It’s a nice screening test. It’s becoming, I think, less useful as people count on digital clocks and have trouble even imagining what an analog clock looks like.”
An approach that is better suited to in-person assessment, but also works by video, is the Poppelreuter figure visual perceptual function test, which is a prompt for the patient that involves common household items overlaying one another “in atypical positions and atypical configurations” where the patient is instructed to describe the items they see on the card. Another approach that works over video is the interlocking finger test, where the patient is asked to copy the hand positions made by the clinician.
Dr. Ovsiew admitted that visuospatial function is nearly impossible to assess over the phone. Asking topographical questions (“If you’re driving from Chicago to Los Angeles, is the Pacific Ocean in front of you, behind you, to your left, or to your right?”) may help judge visuospatial function, but this relies on the patient having the topographic knowledge to answer the questions. Some patients who are topographically disoriented can’t do them at all,” Dr. Ovsiew said.
Bedside neuropsychiatry assesses encoding of a memory, its retention and its retrieval as well as verbal and visual cues. Each one of these aspects of memory can be impaired on its own and should be explored separately, Dr. Ovsiew explained. “Neuropsychiatric clinicians have a rough-and-ready, seat-of-the-pants way of approaching this that wouldn’t pass muster if you’re a psychologist, but is the best we can do at the bedside.”
To test retrieval and retention, the Three Words–Three Shapes test works well in person, with some difficulty by video, and is not possible to administer over the phone. In lieu of that test, giving the patient a simple word list and asking them to repeat the list in order. Using the word list, “these different stages of memory function can be parsed out pretty well at the bedside or chairside, and even by the phone. Figuring out where the memory failure is diagnostically important,” Dr. Ovsiew said.
Executive function, which involves activation, planning, sequencing, maintaining, self-monitoring, and flexible employment of action and attention, is “complicated to evaluate because there are multiple aspects of executive function, multiple deficits that can be seen with executive dysfunction, and they don’t all correlate with each other.”
Within executive function evaluation, the Mental Alternation Test can assess working memory, motor sequencing can be assessed through the ring/fist, fist/edge/palm, alternating fist, and rampart tests. The Go/No-Go test can be used to assess response inhibition. For effortful retrieval evaluation, spontaneous word-list generation – such as thinking of all the items one can buy at a supermarket– can test category fluency, while a task to name all the words starting with a certain letter can assess letter stimulus.
Executive function “is of crucial importance in the neuropsychiatric evaluation because it’s strongly correlated with how well the person functions outside the office,” Dr. Ovsiew said.
Global Academy and this news organization are owned by the same parent company. Dr. Ovsiew reported relationships with Wolters Kluwer Health in the form of consulting, receiving royalty payments, and related activities.
Patients have often been labeled as “poor historians” if they are not able to recollect their own medical history, whether through illness or difficulties in communication. But Fred Ovsiew, MD, speaking at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sees that label as an excuse on the part of the clinician.
“I strongly advise you to drop that phrase from your vocabulary if you do use it, because the patient is not the historian. The doctor, the clinician is the historian,” Dr. Ovsiew said at the meeting, presented by Global Academy for Medical Education. “It is the clinician’s job to put the story together using the account by the patient as one source, but [also] interviewing a collateral informant and/or reviewing records, which is necessary in almost every case of a neuropsychiatric illness.”
Rather, clinicians taking history at the bedside should focus on why the patients cannot give a narrative account of their illness. Patients can have narrative incapacity on a psychogenic basis, such as in patients with conversion or somatoform disorder, he explained. “I think this is a result of the narrative incapacity that develops in people who have had trauma or adverse experiences in childhood and insecure attachment. This is shown on the adult attachment interview as a disorganized account of their childhoods.”
Other patients might not be able to recount their medical history because they are amnestic, which leaves their account vague because of a lack of access to information. “It may be frozen in time in the sense that, up to a certain point in their life, they can recount the history,” Dr. Ovsiew said. “But in recent years, their account becomes vague.”
Patients with right hemisphere lesions might not know that their account has incongruity and is implausible, while patients with dorsolateral prefrontal lesions might be aspontaneous, use few words to describe their situation, and have poor insight. Those with ventromedial prefrontal lesions can be impulsive and have poor insight, not considering alternative possibilities, Dr. Ovsiew noted.
Asking open-ended questions of the patient is the first step to identifying any potential narrative incapacity, followed by a detailed medical history by the clinician. When taking a medical history, try avoiding what Dr. Ovsiew calls the “anything like that?” problem, where a clinician asks a question about a cluster of symptoms that would make sense to a doctor, but not a patient. For example, a doctor might ask whether a patient is experiencing “chest pain or leg swelling – anything like that?” because he or she knows what those symptoms have in common, but the patient might not know the relationship between those symptoms. “You can’t count on the patient to tell you all the relevant information,” he said. “You have to know what to ask about.”
“Patients with brain disease have subtle personality changes, sometimes more obvious personality changes. These need to be inquired about,” Dr. Ovsiew said. “The patient with apathy has reduced negative as well as positive emotions. The patient with depression has reduced positive emotions, but often tells you very clearly about the negative emotions of sadness, guilt. The patient with depression has diurnal variation in mood, a very telling symptom, especially when it’s disclosed spontaneously,” Dr. Ovsiew explained. “The point is, you need to know to ask about it.”
When taking a sleep history, clinicians should be aware of sleep disturbances apart from insomnia and early waking. REM sleep behavior disorder is a condition that should be inquired about. Obstructive sleep apnea is a condition that might not be immediately apparent to the patient, but a bed partner can identify whether a patient has problems breathing throughout the night.
“This is an important condition to uncover for the neuropsychiatrist because it contributes to treatment resistance and depression, and it contributes to cognitive impairment,” Dr. Ovsiew said. “These patients commonly have mild difficulties with attention and concentration.”
Always ask about head injury in every history, which can be relevant to later onset depression, PTSD, and cognitive impairment. Every head injury follows a trajectory of retrograde amnesia and altered state of consciousness (including coma), followed by a period of posttraumatic amnesia. Duration of these states can be used to assess the severity of brain injury, but the 15-point Glasgow Coma Scale is another way to assess injury severity, Dr. Ovsiew explained.
However, the two do not always overlap, he noted. “Someone may have a Glasgow Coma Scale score that is 9-12, predicting moderate brain injury, but they may have a short duration of amnesia. These don’t always follow the same path. There are many different ways of classifying how severe the brain injury is.”
Keep probes brief, straightforward
Cognitive exams of patients with suspected psychiatric disorders should be simple, easy to administer and focused on a single domain of cognition. “Probes should be brief. They should not require specialized equipment. The Purdue Pegboard Test might be a great neuropsychological instrument, but very few of us carry a pegboard around in our medical bags,” Dr. Ovsiew said.
The probe administered should also be accessible to the patient. The serial sevens clinical test, where a patient is asked to repeatedly subtract 7 from 100, is only effective at testing concentration if the patient is capable of completing the test. “There are going to be patients who can’t do the task, but it’s not because of concentration failure, it’s because of subtraction failure,” he said.
When assessing attention, effective tasks include having the patient perform the digit span test forward and backward, count backward from 20 to 1, listing the months of the year in reverse, and performing the Mental Alternation Test. However, Dr. Ovsiew explained there may be some barriers for patients in completing these tasks. “The person may be aphasic and not know the alphabet. The person may have English as a second language and not be skilled at giving the alphabet in English. In some cases, you may want to check and not assume that the patient can count and does know the alphabet.”
In assessing language, listen for aphasic abnormalities. “The patient, of course, is speaking throughout the interview, but you need to take a moment to listen for prosody, to listen to rate of speech, to listen for paraphasic errors or word-finding problems,” Dr. Ovsiew said. Any abnormalities should be probed further through confrontation naming tasks, which can be done in person and with some success through video, but not by phone. Naming to definition (“What do you call the part of a shirt that covers the arm?”) is one way of administering the test over the phone.
Visuospatial function can be assessed by clock drawing but also carries problems. Patients who do not plan their clock before beginning to draw, for example, may have an executive function problem instead of a visuospatial problem, Dr. Ovsiew noted. Patients in whom a clinician suspects hemineglect should be given a visual search task or line by section task. “I like doing clock drawing. It’s a nice screening test. It’s becoming, I think, less useful as people count on digital clocks and have trouble even imagining what an analog clock looks like.”
An approach that is better suited to in-person assessment, but also works by video, is the Poppelreuter figure visual perceptual function test, which is a prompt for the patient that involves common household items overlaying one another “in atypical positions and atypical configurations” where the patient is instructed to describe the items they see on the card. Another approach that works over video is the interlocking finger test, where the patient is asked to copy the hand positions made by the clinician.
Dr. Ovsiew admitted that visuospatial function is nearly impossible to assess over the phone. Asking topographical questions (“If you’re driving from Chicago to Los Angeles, is the Pacific Ocean in front of you, behind you, to your left, or to your right?”) may help judge visuospatial function, but this relies on the patient having the topographic knowledge to answer the questions. Some patients who are topographically disoriented can’t do them at all,” Dr. Ovsiew said.
Bedside neuropsychiatry assesses encoding of a memory, its retention and its retrieval as well as verbal and visual cues. Each one of these aspects of memory can be impaired on its own and should be explored separately, Dr. Ovsiew explained. “Neuropsychiatric clinicians have a rough-and-ready, seat-of-the-pants way of approaching this that wouldn’t pass muster if you’re a psychologist, but is the best we can do at the bedside.”
To test retrieval and retention, the Three Words–Three Shapes test works well in person, with some difficulty by video, and is not possible to administer over the phone. In lieu of that test, giving the patient a simple word list and asking them to repeat the list in order. Using the word list, “these different stages of memory function can be parsed out pretty well at the bedside or chairside, and even by the phone. Figuring out where the memory failure is diagnostically important,” Dr. Ovsiew said.
Executive function, which involves activation, planning, sequencing, maintaining, self-monitoring, and flexible employment of action and attention, is “complicated to evaluate because there are multiple aspects of executive function, multiple deficits that can be seen with executive dysfunction, and they don’t all correlate with each other.”
Within executive function evaluation, the Mental Alternation Test can assess working memory, motor sequencing can be assessed through the ring/fist, fist/edge/palm, alternating fist, and rampart tests. The Go/No-Go test can be used to assess response inhibition. For effortful retrieval evaluation, spontaneous word-list generation – such as thinking of all the items one can buy at a supermarket– can test category fluency, while a task to name all the words starting with a certain letter can assess letter stimulus.
Executive function “is of crucial importance in the neuropsychiatric evaluation because it’s strongly correlated with how well the person functions outside the office,” Dr. Ovsiew said.
Global Academy and this news organization are owned by the same parent company. Dr. Ovsiew reported relationships with Wolters Kluwer Health in the form of consulting, receiving royalty payments, and related activities.
FROM FOCUS ON NEUROPSYCHIATRY 2020
COVID-19 linked to development of myasthenia gravis
Myasthenia gravis should be added to the growing list of potential neurological sequelae associated with COVID-19, new research suggests. Clinicians from Italy have described what they believe are
“I think it is possible that there could be many more cases,” said lead author Domenico Restivo, MD, of the Garibaldi Hospital, Catania, Italy. “In fact, myasthenia gravis could be underestimated especially in the course of COVID-19 infection in which a specific muscular weakness is frequently present. For this reason, this association is easy to miss if not top of mind,” Dr. Restivo said.
None of the three patients had previous neurologic or autoimmune disorders. In all three cases, symptoms of myasthenia gravis appeared within 5-7 days after onset of fever caused by SARS-CoV-2 infection. The time from presumed SARS-CoV-2 infection to myasthenia gravis symptoms “is consistent with the time from infection to symptoms in other neurologic disorders triggered by infections,” the investigators reported.
The findings were published online August 10 in Annals of Internal Medicine.
First patients
The first patient described in the report was a 64-year-old man who had a fever as high as 39° C (102.2° F) for 4 days. Five days after fever onset, he developed diplopia and muscle fatigue. The patient’s neurologic examination was “unremarkable.” Computed tomography (CT) of the thorax excluded thymoma, and findings on chest radiograph were normal. He tested positive for SARS-CoV-2 on nasopharyngeal swab and real-time reverse transcriptase polymerase chain reaction (RT-PCR).
The patient’s symptoms led the investigators to suspect myasthenia gravis. Repetitive stimulation of the patient’s facial nerve showed a 57% decrement, confirming involvement of the postsynaptic neuromuscular junction. The concentration of AChR antibodies in serum was also elevated (22.8 pmol/L; reference range, <0.4 pmol/L). The patient was treated with pyridostigmine bromide and prednisone and had a response “typical for someone with myasthenia gravis,” the researchers wrote.
The second patient was a 68-year-old man who had a fever as high as 38.8° C (101.8° F) for 7 days. On day 7, he developed muscle fatigue, diplopia, and dysphagia. Findings of a chest CT and neurologic exam were normal. Nasopharyngeal swab and RT-PCR testing for COVID-19 were positive. As with the first patient, myasthenia gravis was suspected because of the patient’s symptoms. Repetitive nerve stimulation revealed a postsynaptic deficit of neuromuscular transmission of the facial (52%) and ulnar (21%) nerves. His serum AChR antibody level was elevated (27.6 pmol/L). The patient improved after one cycle of intravenous immunoglobulin treatment.
Possible mechanisms
The third patient was a 71-year-old woman with cough and a fever up to 38.6° C (101.5° F) for 6 days. She initially tested negative for SARS-CoV-2 on nasopharyngeal swab and RT-PCR. Five days after her symptoms began, she developed bilateral ocular ptosis, diplopia, and hypophonia. CT of the thorax excluded thymoma but showed bilateral interstitial pneumonia. On day 6, she developed dysphagia and respiratory failure, and was transferred to the ICU where she received mechanical ventilation.
Repetitive nerve stimulation revealed a postsynaptic deficit of neuromuscular transmission of the ulnar nerve (56%), and her serum AChR antibody level was elevated (35.6 pmol/L). Five days later, a second nasopharyngeal swab test for SARS-CoV-2 was positive. The patient improved following plasmapheresis treatment and was successfully extubated.
The investigators noted that this patient received hydroxychloroquine the day after the onset of neurologic symptoms, but the drug was withdrawn a day later, so they do not believe that it caused the symptoms of myasthenia gravis.
The observations in these three patients are “consistent with reports of other infections that induce autoimmune disorders, as well as with the growing evidence of other neurologic disorders with presumed autoimmune mechanisms after COVID-19 onset,” the researchers wrote.
They offered several possible explanations for the link between COVID-19 and myasthenia gravis. “Antibodies that are directed against SARS-CoV-2 proteins may cross-react with AChR subunits, because the virus has epitopes that are similar to components of the neuromuscular junction; this is known to occur in other neurologic autoimmune disorders after infection. Alternatively, COVID-19 infection may break immunologic self-tolerance,” the investigators wrote.
“The main message for clinicians is that myasthenia gravis, as well as other neurological disorders associated with autoimmunity, could occur in the course of SARS-CoV-2 infection,” Dr. Restivo said. Prompt recognition of the disease “could lead to a drug treatment that limits its evolution as quickly as possible,” he added.
An “unmasking”
Commenting on the findings, Anthony Geraci, MD, director of neuromuscular medicine, Northwell Health, Great Neck, N.Y., said these case reports of myasthenia gravis after SARS-CoV-2 infection are “not unique or novel as there has been a long understanding that seropositive [AChR antibody-positive] myasthenia gravis can and is frequently ‘unmasked’ in the setting” of several viral and bacterial infections.
“Antibodies in myasthenia gravis are of a type that take several weeks to develop to measurable levels as in the reported cases by Restivo et al., giving strong support to the notion that subclinical myasthenia gravis can be immunologically upregulated in the setting of viral infection and this is a far more likely explanation of the observed association reported,” added Dr. Geraci, who was not involved with the research.
He noted that, at his institution, “we have also observed ocular myasthenia gravis emerge in patients with SARS-CoV-2 infection, with similar double vision and lid droop, as we have seen similarly in patients with Zika, West Nile, and other viral infections, as well as a multiplicity of bacterial infections.”
“Most of our observed patients have responded to treatment much the same as reported by the three cases from Restivo and colleagues,” Dr.Geraci reported.
The authors of the study disclosed no conflicts of interest.
A version of this article originally appeared on Medscape.com.
Myasthenia gravis should be added to the growing list of potential neurological sequelae associated with COVID-19, new research suggests. Clinicians from Italy have described what they believe are
“I think it is possible that there could be many more cases,” said lead author Domenico Restivo, MD, of the Garibaldi Hospital, Catania, Italy. “In fact, myasthenia gravis could be underestimated especially in the course of COVID-19 infection in which a specific muscular weakness is frequently present. For this reason, this association is easy to miss if not top of mind,” Dr. Restivo said.
None of the three patients had previous neurologic or autoimmune disorders. In all three cases, symptoms of myasthenia gravis appeared within 5-7 days after onset of fever caused by SARS-CoV-2 infection. The time from presumed SARS-CoV-2 infection to myasthenia gravis symptoms “is consistent with the time from infection to symptoms in other neurologic disorders triggered by infections,” the investigators reported.
The findings were published online August 10 in Annals of Internal Medicine.
First patients
The first patient described in the report was a 64-year-old man who had a fever as high as 39° C (102.2° F) for 4 days. Five days after fever onset, he developed diplopia and muscle fatigue. The patient’s neurologic examination was “unremarkable.” Computed tomography (CT) of the thorax excluded thymoma, and findings on chest radiograph were normal. He tested positive for SARS-CoV-2 on nasopharyngeal swab and real-time reverse transcriptase polymerase chain reaction (RT-PCR).
The patient’s symptoms led the investigators to suspect myasthenia gravis. Repetitive stimulation of the patient’s facial nerve showed a 57% decrement, confirming involvement of the postsynaptic neuromuscular junction. The concentration of AChR antibodies in serum was also elevated (22.8 pmol/L; reference range, <0.4 pmol/L). The patient was treated with pyridostigmine bromide and prednisone and had a response “typical for someone with myasthenia gravis,” the researchers wrote.
The second patient was a 68-year-old man who had a fever as high as 38.8° C (101.8° F) for 7 days. On day 7, he developed muscle fatigue, diplopia, and dysphagia. Findings of a chest CT and neurologic exam were normal. Nasopharyngeal swab and RT-PCR testing for COVID-19 were positive. As with the first patient, myasthenia gravis was suspected because of the patient’s symptoms. Repetitive nerve stimulation revealed a postsynaptic deficit of neuromuscular transmission of the facial (52%) and ulnar (21%) nerves. His serum AChR antibody level was elevated (27.6 pmol/L). The patient improved after one cycle of intravenous immunoglobulin treatment.
Possible mechanisms
The third patient was a 71-year-old woman with cough and a fever up to 38.6° C (101.5° F) for 6 days. She initially tested negative for SARS-CoV-2 on nasopharyngeal swab and RT-PCR. Five days after her symptoms began, she developed bilateral ocular ptosis, diplopia, and hypophonia. CT of the thorax excluded thymoma but showed bilateral interstitial pneumonia. On day 6, she developed dysphagia and respiratory failure, and was transferred to the ICU where she received mechanical ventilation.
Repetitive nerve stimulation revealed a postsynaptic deficit of neuromuscular transmission of the ulnar nerve (56%), and her serum AChR antibody level was elevated (35.6 pmol/L). Five days later, a second nasopharyngeal swab test for SARS-CoV-2 was positive. The patient improved following plasmapheresis treatment and was successfully extubated.
The investigators noted that this patient received hydroxychloroquine the day after the onset of neurologic symptoms, but the drug was withdrawn a day later, so they do not believe that it caused the symptoms of myasthenia gravis.
The observations in these three patients are “consistent with reports of other infections that induce autoimmune disorders, as well as with the growing evidence of other neurologic disorders with presumed autoimmune mechanisms after COVID-19 onset,” the researchers wrote.
They offered several possible explanations for the link between COVID-19 and myasthenia gravis. “Antibodies that are directed against SARS-CoV-2 proteins may cross-react with AChR subunits, because the virus has epitopes that are similar to components of the neuromuscular junction; this is known to occur in other neurologic autoimmune disorders after infection. Alternatively, COVID-19 infection may break immunologic self-tolerance,” the investigators wrote.
“The main message for clinicians is that myasthenia gravis, as well as other neurological disorders associated with autoimmunity, could occur in the course of SARS-CoV-2 infection,” Dr. Restivo said. Prompt recognition of the disease “could lead to a drug treatment that limits its evolution as quickly as possible,” he added.
An “unmasking”
Commenting on the findings, Anthony Geraci, MD, director of neuromuscular medicine, Northwell Health, Great Neck, N.Y., said these case reports of myasthenia gravis after SARS-CoV-2 infection are “not unique or novel as there has been a long understanding that seropositive [AChR antibody-positive] myasthenia gravis can and is frequently ‘unmasked’ in the setting” of several viral and bacterial infections.
“Antibodies in myasthenia gravis are of a type that take several weeks to develop to measurable levels as in the reported cases by Restivo et al., giving strong support to the notion that subclinical myasthenia gravis can be immunologically upregulated in the setting of viral infection and this is a far more likely explanation of the observed association reported,” added Dr. Geraci, who was not involved with the research.
He noted that, at his institution, “we have also observed ocular myasthenia gravis emerge in patients with SARS-CoV-2 infection, with similar double vision and lid droop, as we have seen similarly in patients with Zika, West Nile, and other viral infections, as well as a multiplicity of bacterial infections.”
“Most of our observed patients have responded to treatment much the same as reported by the three cases from Restivo and colleagues,” Dr.Geraci reported.
The authors of the study disclosed no conflicts of interest.
A version of this article originally appeared on Medscape.com.
Myasthenia gravis should be added to the growing list of potential neurological sequelae associated with COVID-19, new research suggests. Clinicians from Italy have described what they believe are
“I think it is possible that there could be many more cases,” said lead author Domenico Restivo, MD, of the Garibaldi Hospital, Catania, Italy. “In fact, myasthenia gravis could be underestimated especially in the course of COVID-19 infection in which a specific muscular weakness is frequently present. For this reason, this association is easy to miss if not top of mind,” Dr. Restivo said.
None of the three patients had previous neurologic or autoimmune disorders. In all three cases, symptoms of myasthenia gravis appeared within 5-7 days after onset of fever caused by SARS-CoV-2 infection. The time from presumed SARS-CoV-2 infection to myasthenia gravis symptoms “is consistent with the time from infection to symptoms in other neurologic disorders triggered by infections,” the investigators reported.
The findings were published online August 10 in Annals of Internal Medicine.
First patients
The first patient described in the report was a 64-year-old man who had a fever as high as 39° C (102.2° F) for 4 days. Five days after fever onset, he developed diplopia and muscle fatigue. The patient’s neurologic examination was “unremarkable.” Computed tomography (CT) of the thorax excluded thymoma, and findings on chest radiograph were normal. He tested positive for SARS-CoV-2 on nasopharyngeal swab and real-time reverse transcriptase polymerase chain reaction (RT-PCR).
The patient’s symptoms led the investigators to suspect myasthenia gravis. Repetitive stimulation of the patient’s facial nerve showed a 57% decrement, confirming involvement of the postsynaptic neuromuscular junction. The concentration of AChR antibodies in serum was also elevated (22.8 pmol/L; reference range, <0.4 pmol/L). The patient was treated with pyridostigmine bromide and prednisone and had a response “typical for someone with myasthenia gravis,” the researchers wrote.
The second patient was a 68-year-old man who had a fever as high as 38.8° C (101.8° F) for 7 days. On day 7, he developed muscle fatigue, diplopia, and dysphagia. Findings of a chest CT and neurologic exam were normal. Nasopharyngeal swab and RT-PCR testing for COVID-19 were positive. As with the first patient, myasthenia gravis was suspected because of the patient’s symptoms. Repetitive nerve stimulation revealed a postsynaptic deficit of neuromuscular transmission of the facial (52%) and ulnar (21%) nerves. His serum AChR antibody level was elevated (27.6 pmol/L). The patient improved after one cycle of intravenous immunoglobulin treatment.
Possible mechanisms
The third patient was a 71-year-old woman with cough and a fever up to 38.6° C (101.5° F) for 6 days. She initially tested negative for SARS-CoV-2 on nasopharyngeal swab and RT-PCR. Five days after her symptoms began, she developed bilateral ocular ptosis, diplopia, and hypophonia. CT of the thorax excluded thymoma but showed bilateral interstitial pneumonia. On day 6, she developed dysphagia and respiratory failure, and was transferred to the ICU where she received mechanical ventilation.
Repetitive nerve stimulation revealed a postsynaptic deficit of neuromuscular transmission of the ulnar nerve (56%), and her serum AChR antibody level was elevated (35.6 pmol/L). Five days later, a second nasopharyngeal swab test for SARS-CoV-2 was positive. The patient improved following plasmapheresis treatment and was successfully extubated.
The investigators noted that this patient received hydroxychloroquine the day after the onset of neurologic symptoms, but the drug was withdrawn a day later, so they do not believe that it caused the symptoms of myasthenia gravis.
The observations in these three patients are “consistent with reports of other infections that induce autoimmune disorders, as well as with the growing evidence of other neurologic disorders with presumed autoimmune mechanisms after COVID-19 onset,” the researchers wrote.
They offered several possible explanations for the link between COVID-19 and myasthenia gravis. “Antibodies that are directed against SARS-CoV-2 proteins may cross-react with AChR subunits, because the virus has epitopes that are similar to components of the neuromuscular junction; this is known to occur in other neurologic autoimmune disorders after infection. Alternatively, COVID-19 infection may break immunologic self-tolerance,” the investigators wrote.
“The main message for clinicians is that myasthenia gravis, as well as other neurological disorders associated with autoimmunity, could occur in the course of SARS-CoV-2 infection,” Dr. Restivo said. Prompt recognition of the disease “could lead to a drug treatment that limits its evolution as quickly as possible,” he added.
An “unmasking”
Commenting on the findings, Anthony Geraci, MD, director of neuromuscular medicine, Northwell Health, Great Neck, N.Y., said these case reports of myasthenia gravis after SARS-CoV-2 infection are “not unique or novel as there has been a long understanding that seropositive [AChR antibody-positive] myasthenia gravis can and is frequently ‘unmasked’ in the setting” of several viral and bacterial infections.
“Antibodies in myasthenia gravis are of a type that take several weeks to develop to measurable levels as in the reported cases by Restivo et al., giving strong support to the notion that subclinical myasthenia gravis can be immunologically upregulated in the setting of viral infection and this is a far more likely explanation of the observed association reported,” added Dr. Geraci, who was not involved with the research.
He noted that, at his institution, “we have also observed ocular myasthenia gravis emerge in patients with SARS-CoV-2 infection, with similar double vision and lid droop, as we have seen similarly in patients with Zika, West Nile, and other viral infections, as well as a multiplicity of bacterial infections.”
“Most of our observed patients have responded to treatment much the same as reported by the three cases from Restivo and colleagues,” Dr.Geraci reported.
The authors of the study disclosed no conflicts of interest.
A version of this article originally appeared on Medscape.com.
ADHD and dyslexia may affect evaluation of concussion
, a new study shows.
“Our results suggest kids with certain learning disorders may respond differently to concussion tests, and this needs to be taken into account when advising on recovery times and when they can return to sport,” said lead author Mathew Stokes, MD. Dr. Stokes is assistant professor of pediatrics and neurology/neurotherapeutics at the University of Texas–Southwestern Medical Center, Dallas.
The study was presented at the American Academy of Neurology Sports Concussion Virtual Conference, held online July 31 to Aug. 1.
Learning disorders affected scores
The researchers analyzed data from participants aged 10-18 years who were enrolled in the North Texas Concussion Registry (ConTex). Participants had been diagnosed with a concussion that was sustained within 30 days of enrollment. The researchers investigated whether there were differences between patients who had no history of learning disorders and those with a history of dyslexia and/or ADD/ADHD with regard to results of clinical testing following concussion.
Of the 1,298 individuals in the study, 58 had been diagnosed with dyslexia, 158 had been diagnosed with ADD/ADHD, and 35 had been diagnosed with both conditions. There was no difference in age, time since injury, or history of concussion between those with learning disorders and those without, but there were more male patients in the ADD/ADHD group.
Results showed that in the dyslexia group, mean time was slower (P = .011), and there was an increase in error scores on the King-Devick (KD) test (P = .028). That test assesses eye movements and involves the rapid naming of numbers that are spaced differently. In addition, those with ADD/ADHD had significantly higher impulse control scores (P = .007) on the ImPACT series of tests, which are commonly used in the evaluation of concussion. Participants with both dyslexia and ADHD demonstrated slower KD times (P = .009) and had higher depression scores and anxiety scores.
Dr. Stokes noted that a limiting factor of the study was that baseline scores were not available. “It is possible that kids with ADD have less impulse control even at baseline, and this would need to be taken into account,” he said. “You may perhaps also expect someone with dyslexia to have a worse score on the KD tests, so we need more data on how these scores are affected from baseline in these individuals. But our results show that when evaluating kids pre- or post concussion, it is important to know about learning disorders, as this will affect how we interpret the data.”
At 3-month follow-up, there were no longer significant differences in anxiety and depression scores for those with and those without learning disorders. “This suggests anxiety and depression may well be worse temporarily after concussion for those with ADD/ADHD but gets better with time,” Dr. Stokes said.
Follow-up data were not available for the other cognitive tests.
Are recovery times longer?
Asked whether young people with these learning disorders needed a longer time to recover after concussion, Dr. Stokes said: “That is a million-dollar question. Studies so far on this have shown conflicting results. Our results add to a growing body of literature on this.” He stressed that it is important to include anxiety and depression scores on both baseline and postconcussion tests. “People don’t tend to think of these symptoms as being associated with concussion, but they are actually very prominent in this situation,” he noted. “Our results suggest that individuals with ADHD may be more prone to anxiety and depression, and a blow to the head may tip them more into these symptoms.”
Discussing the study at a virtual press conference as part of the AAN Sports Concussion meeting, the codirector of the meeting, David Dodick, MD, Mayo Clinic, Scottsdale, Ariz., said: “This is a very interesting and important study which suggests there are differences between adolescents with a history of dyslexia/ADHD and those without these conditions in performance in concussion tests. Understanding the differences in these groups will help health care providers in evaluating these athletes and assisting in counseling them and their families with regard to their risk of injury.
“It is important to recognize that athletes with ADHD, whether or not they are on medication, may take longer to recover from a concussion,” Dr. Dodick added. They also exhibit greater reductions in cognitive skills and visual motor speed regarding hand-eye coordination, he said. There is an increase in the severity of symptoms. “Symptoms that exist in both groups tend to more severe in those individuals with ADHD,” he noted.
“Ascertaining the presence or absence of ADHD or dyslexia in those who are participating in sport is important, especially when trying to interpret the results of baseline testing, the results of postinjury testing, decisions on when to return to play, and assessing for individuals and their families the risk of long-term repeat concussions and adverse outcomes,” he concluded.
The other codirector of the AAN meeting, Brian Hainline, MD, chief medical officer of the National Collegiate Athletic Association, added: “It appears that athletes with ADHD may suffer more with concussion and have a longer recovery time. This can inform our decision making and help these individuals to understand that they are at higher risk.”
Dr. Hainline said this raises another important point: “Concussion is not a homogeneous entity. It is a brain injury that can manifest in multiple parts of the brain, and the way the brain is from a premorbid or comorbid point of view can influence the manifestation of concussion as well,” he said. “All these things need to be taken into account.”
Attentional deficit may itself make an individual more susceptible to sustaining an injury in the first place, he said. “All of this is an evolving body of research which is helping clinicians to make better-informed decisions for athletes who may manifest differently.”
A version of this article originally appeared on Medscape.com.
, a new study shows.
“Our results suggest kids with certain learning disorders may respond differently to concussion tests, and this needs to be taken into account when advising on recovery times and when they can return to sport,” said lead author Mathew Stokes, MD. Dr. Stokes is assistant professor of pediatrics and neurology/neurotherapeutics at the University of Texas–Southwestern Medical Center, Dallas.
The study was presented at the American Academy of Neurology Sports Concussion Virtual Conference, held online July 31 to Aug. 1.
Learning disorders affected scores
The researchers analyzed data from participants aged 10-18 years who were enrolled in the North Texas Concussion Registry (ConTex). Participants had been diagnosed with a concussion that was sustained within 30 days of enrollment. The researchers investigated whether there were differences between patients who had no history of learning disorders and those with a history of dyslexia and/or ADD/ADHD with regard to results of clinical testing following concussion.
Of the 1,298 individuals in the study, 58 had been diagnosed with dyslexia, 158 had been diagnosed with ADD/ADHD, and 35 had been diagnosed with both conditions. There was no difference in age, time since injury, or history of concussion between those with learning disorders and those without, but there were more male patients in the ADD/ADHD group.
Results showed that in the dyslexia group, mean time was slower (P = .011), and there was an increase in error scores on the King-Devick (KD) test (P = .028). That test assesses eye movements and involves the rapid naming of numbers that are spaced differently. In addition, those with ADD/ADHD had significantly higher impulse control scores (P = .007) on the ImPACT series of tests, which are commonly used in the evaluation of concussion. Participants with both dyslexia and ADHD demonstrated slower KD times (P = .009) and had higher depression scores and anxiety scores.
Dr. Stokes noted that a limiting factor of the study was that baseline scores were not available. “It is possible that kids with ADD have less impulse control even at baseline, and this would need to be taken into account,” he said. “You may perhaps also expect someone with dyslexia to have a worse score on the KD tests, so we need more data on how these scores are affected from baseline in these individuals. But our results show that when evaluating kids pre- or post concussion, it is important to know about learning disorders, as this will affect how we interpret the data.”
At 3-month follow-up, there were no longer significant differences in anxiety and depression scores for those with and those without learning disorders. “This suggests anxiety and depression may well be worse temporarily after concussion for those with ADD/ADHD but gets better with time,” Dr. Stokes said.
Follow-up data were not available for the other cognitive tests.
Are recovery times longer?
Asked whether young people with these learning disorders needed a longer time to recover after concussion, Dr. Stokes said: “That is a million-dollar question. Studies so far on this have shown conflicting results. Our results add to a growing body of literature on this.” He stressed that it is important to include anxiety and depression scores on both baseline and postconcussion tests. “People don’t tend to think of these symptoms as being associated with concussion, but they are actually very prominent in this situation,” he noted. “Our results suggest that individuals with ADHD may be more prone to anxiety and depression, and a blow to the head may tip them more into these symptoms.”
Discussing the study at a virtual press conference as part of the AAN Sports Concussion meeting, the codirector of the meeting, David Dodick, MD, Mayo Clinic, Scottsdale, Ariz., said: “This is a very interesting and important study which suggests there are differences between adolescents with a history of dyslexia/ADHD and those without these conditions in performance in concussion tests. Understanding the differences in these groups will help health care providers in evaluating these athletes and assisting in counseling them and their families with regard to their risk of injury.
“It is important to recognize that athletes with ADHD, whether or not they are on medication, may take longer to recover from a concussion,” Dr. Dodick added. They also exhibit greater reductions in cognitive skills and visual motor speed regarding hand-eye coordination, he said. There is an increase in the severity of symptoms. “Symptoms that exist in both groups tend to more severe in those individuals with ADHD,” he noted.
“Ascertaining the presence or absence of ADHD or dyslexia in those who are participating in sport is important, especially when trying to interpret the results of baseline testing, the results of postinjury testing, decisions on when to return to play, and assessing for individuals and their families the risk of long-term repeat concussions and adverse outcomes,” he concluded.
The other codirector of the AAN meeting, Brian Hainline, MD, chief medical officer of the National Collegiate Athletic Association, added: “It appears that athletes with ADHD may suffer more with concussion and have a longer recovery time. This can inform our decision making and help these individuals to understand that they are at higher risk.”
Dr. Hainline said this raises another important point: “Concussion is not a homogeneous entity. It is a brain injury that can manifest in multiple parts of the brain, and the way the brain is from a premorbid or comorbid point of view can influence the manifestation of concussion as well,” he said. “All these things need to be taken into account.”
Attentional deficit may itself make an individual more susceptible to sustaining an injury in the first place, he said. “All of this is an evolving body of research which is helping clinicians to make better-informed decisions for athletes who may manifest differently.”
A version of this article originally appeared on Medscape.com.
, a new study shows.
“Our results suggest kids with certain learning disorders may respond differently to concussion tests, and this needs to be taken into account when advising on recovery times and when they can return to sport,” said lead author Mathew Stokes, MD. Dr. Stokes is assistant professor of pediatrics and neurology/neurotherapeutics at the University of Texas–Southwestern Medical Center, Dallas.
The study was presented at the American Academy of Neurology Sports Concussion Virtual Conference, held online July 31 to Aug. 1.
Learning disorders affected scores
The researchers analyzed data from participants aged 10-18 years who were enrolled in the North Texas Concussion Registry (ConTex). Participants had been diagnosed with a concussion that was sustained within 30 days of enrollment. The researchers investigated whether there were differences between patients who had no history of learning disorders and those with a history of dyslexia and/or ADD/ADHD with regard to results of clinical testing following concussion.
Of the 1,298 individuals in the study, 58 had been diagnosed with dyslexia, 158 had been diagnosed with ADD/ADHD, and 35 had been diagnosed with both conditions. There was no difference in age, time since injury, or history of concussion between those with learning disorders and those without, but there were more male patients in the ADD/ADHD group.
Results showed that in the dyslexia group, mean time was slower (P = .011), and there was an increase in error scores on the King-Devick (KD) test (P = .028). That test assesses eye movements and involves the rapid naming of numbers that are spaced differently. In addition, those with ADD/ADHD had significantly higher impulse control scores (P = .007) on the ImPACT series of tests, which are commonly used in the evaluation of concussion. Participants with both dyslexia and ADHD demonstrated slower KD times (P = .009) and had higher depression scores and anxiety scores.
Dr. Stokes noted that a limiting factor of the study was that baseline scores were not available. “It is possible that kids with ADD have less impulse control even at baseline, and this would need to be taken into account,” he said. “You may perhaps also expect someone with dyslexia to have a worse score on the KD tests, so we need more data on how these scores are affected from baseline in these individuals. But our results show that when evaluating kids pre- or post concussion, it is important to know about learning disorders, as this will affect how we interpret the data.”
At 3-month follow-up, there were no longer significant differences in anxiety and depression scores for those with and those without learning disorders. “This suggests anxiety and depression may well be worse temporarily after concussion for those with ADD/ADHD but gets better with time,” Dr. Stokes said.
Follow-up data were not available for the other cognitive tests.
Are recovery times longer?
Asked whether young people with these learning disorders needed a longer time to recover after concussion, Dr. Stokes said: “That is a million-dollar question. Studies so far on this have shown conflicting results. Our results add to a growing body of literature on this.” He stressed that it is important to include anxiety and depression scores on both baseline and postconcussion tests. “People don’t tend to think of these symptoms as being associated with concussion, but they are actually very prominent in this situation,” he noted. “Our results suggest that individuals with ADHD may be more prone to anxiety and depression, and a blow to the head may tip them more into these symptoms.”
Discussing the study at a virtual press conference as part of the AAN Sports Concussion meeting, the codirector of the meeting, David Dodick, MD, Mayo Clinic, Scottsdale, Ariz., said: “This is a very interesting and important study which suggests there are differences between adolescents with a history of dyslexia/ADHD and those without these conditions in performance in concussion tests. Understanding the differences in these groups will help health care providers in evaluating these athletes and assisting in counseling them and their families with regard to their risk of injury.
“It is important to recognize that athletes with ADHD, whether or not they are on medication, may take longer to recover from a concussion,” Dr. Dodick added. They also exhibit greater reductions in cognitive skills and visual motor speed regarding hand-eye coordination, he said. There is an increase in the severity of symptoms. “Symptoms that exist in both groups tend to more severe in those individuals with ADHD,” he noted.
“Ascertaining the presence or absence of ADHD or dyslexia in those who are participating in sport is important, especially when trying to interpret the results of baseline testing, the results of postinjury testing, decisions on when to return to play, and assessing for individuals and their families the risk of long-term repeat concussions and adverse outcomes,” he concluded.
The other codirector of the AAN meeting, Brian Hainline, MD, chief medical officer of the National Collegiate Athletic Association, added: “It appears that athletes with ADHD may suffer more with concussion and have a longer recovery time. This can inform our decision making and help these individuals to understand that they are at higher risk.”
Dr. Hainline said this raises another important point: “Concussion is not a homogeneous entity. It is a brain injury that can manifest in multiple parts of the brain, and the way the brain is from a premorbid or comorbid point of view can influence the manifestation of concussion as well,” he said. “All these things need to be taken into account.”
Attentional deficit may itself make an individual more susceptible to sustaining an injury in the first place, he said. “All of this is an evolving body of research which is helping clinicians to make better-informed decisions for athletes who may manifest differently.”
A version of this article originally appeared on Medscape.com.
From AAN Sports Concussion Conference
More evidence links gum disease and dementia risk
especially in those with severe gum inflammation and edentulism, new research suggests.
Over a 20-year period, investigators prospectively followed more than 8,000 individuals aged around 63 years who did not have cognitive impairment or dementia at baseline, grouping them based on the extent and severity of their periodontal disease and number of lost teeth.
Results showed that 14% of participants with healthy gums and all their teeth at baseline developed dementia, compared with 18% of those with mild periodontal disease and 22% who had severe periodontal disease. The highest percentage (23%) of participants who developed dementia was found in those who were edentulous.
After accounting for comorbidities that might affect dementia risk, edentulous participants had a 20% higher risk for developing MCI or dementia, compared with the healthy group.
Because the study was observational, “we don’t have knowledge of causality so we cannot state that if you treat periodontal disease you can prevent or treat dementia,” said lead author Ryan T. Demmer, PhD, MPH, associate professor, division of epidemiology and community health, University of Minnesota, Minneapolis. However, “the take-home message from this paper is that it further supports the possibility that oral infections could be a risk factor for dementia.”
The study was published online July 29 in Neurology.
The ARIC trial
Prior studies have “described the interrelation of tooth loss or periodontal disease and cognitive outcomes, although many reports were cross-sectional or case-control … and often lacked robust confounder adjustment,” the investigators noted. Additionally, lack of longitudinal data impedes the “potential for baseline periodontal status to predict incident MCI.”
To explore the associations between periodontal status and incident MCI and dementia, the researchers studied participants in the ARIC study, a community-based longitudinal cohort consisting of 15,792 predominantly Black and White participants aged 45-64 years. The current analysis included 8,275 individuals (55% women; 21% black; mean age, 63 years) who at baseline did not meet criteria for dementia or MCI.
A full-mouth periodontal examination was conducted at baseline and participants were categorized according to the severity and extent of gingival inflammation and tooth attachment loss based on the Periodontal Profile Class (PPC) seven-category model. Potential confounding variables included age, race, education level, physical activity, smoking status, oral hygiene and access to care, plasma lipid levels, APOE genotype, body mass index, blood pressure, type 2 diabetes, and heart failure.
Based on PPC categorization, 22% of the patients had healthy gums, 12% had mild periodontal disease, 8% had a high gingival inflammation index, and 12% had posterior disease (with 6% having severe disease). In addition, 9% had tooth loss, 11% had severe tooth loss, and 20% were edentulous.
Infection hypothesis
Results showed that participants with worse periodontal status were more likely to have risk factors for vascular disease and dementia, such as smoking, hypertension, diabetes, and coronary heart disease. During median follow-up of 18.4 years, 19% of participants overall (n = 1,569) developed dementia, translating into 11.8 cases per 1,000 person-years. There were notable differences between the PPC categories in rates of incident dementia, with edentulous participants at twice the risk for developing dementia, compared with those who had healthy gums.
For participants with severe PPC, including severe tooth loss and severe disease, the multivariable-adjusted hazard ratio for incident dementia was 1.22 (95% confidence interval, 1.01-1.47) versus those who were periodontally healthy. For participants with edentulism, the HR was 1.21 (95% CI, 0.99-1.48). The adjusted risk ratios for the combined dementia/MCI outcome among participants with mild to intermediate PPC, severe PPC, or edentulism versus the periodontal healthy group were 1.22 (95% CI, 1.00-1.48), 1.15 (95% CI, 0.88-1.51), and 1.90 (95% CI, 1.40-2.58), respectively.
These findings were most pronounced among younger (median age at dental exam, younger than 62) versus older (62 years and older) participants (P = .02). Severe disease or total tooth loss were associated with an approximately 20% greater dementia incidence during the follow-up period, compared with healthy gums.
The investigators noted that the findings were “generally consistent” when considering the combined outcome of MCI and dementia. However, they noted that the association between edentulism and MCI was “markedly stronger,” with an approximate 100% increase in MCI or MCI plus dementia.
The association between periodontal disease and MCI or dementia “is rooted in the infection hypothesis, meaning adverse microbial exposures in the mucosal surfaces of the mouth, especially the subgingival space,” Dr. Demmer said. “One notion is that there could somehow be a direct infection of the brain with oral organisms, which posits that the oral organism could travel to the brain, colonize there, and cause damage that impairs cognition.”
Another possible mechanism is that chronic systemic inflammation in response to oral infections can eventually lead to vascular disease which, in turn, is a known risk factor for future dementia, he noted.
“Brush and floss”
Commenting on the research findings, James M. Noble, MD, associate professor of neurology, Taub Institute for Research on Alzheimer’s and the Aging Brain, Columbia University, New York, called the study “well characterized both by whole-mouth assessments and cognitive assessments performed in a standardized manner.” Moreover, “the study was sufficiently sized to allow for exploration of age and suggests that oral health may be a more important factor earlier in the course of aging, in late adulthood,” said Dr. Noble, who was not involved with the research.
The study also “makes an important contribution to this field through a rigorously followed cohort and robust design for both periodontal predictor and cognitive outcome assessments,” he said, noting that, “as always, the take-home message is ‘brush and floss.’
“Although we don’t know if treating periodontal disease can help treat dementia, this study suggests that we have to pay attention to good oral hygiene and make referrals to dentists when appropriate,” Dr. Demmer added.
The ARIC trial is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute. Dr. Demmer, the study coauthors, and Dr. Noble have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
especially in those with severe gum inflammation and edentulism, new research suggests.
Over a 20-year period, investigators prospectively followed more than 8,000 individuals aged around 63 years who did not have cognitive impairment or dementia at baseline, grouping them based on the extent and severity of their periodontal disease and number of lost teeth.
Results showed that 14% of participants with healthy gums and all their teeth at baseline developed dementia, compared with 18% of those with mild periodontal disease and 22% who had severe periodontal disease. The highest percentage (23%) of participants who developed dementia was found in those who were edentulous.
After accounting for comorbidities that might affect dementia risk, edentulous participants had a 20% higher risk for developing MCI or dementia, compared with the healthy group.
Because the study was observational, “we don’t have knowledge of causality so we cannot state that if you treat periodontal disease you can prevent or treat dementia,” said lead author Ryan T. Demmer, PhD, MPH, associate professor, division of epidemiology and community health, University of Minnesota, Minneapolis. However, “the take-home message from this paper is that it further supports the possibility that oral infections could be a risk factor for dementia.”
The study was published online July 29 in Neurology.
The ARIC trial
Prior studies have “described the interrelation of tooth loss or periodontal disease and cognitive outcomes, although many reports were cross-sectional or case-control … and often lacked robust confounder adjustment,” the investigators noted. Additionally, lack of longitudinal data impedes the “potential for baseline periodontal status to predict incident MCI.”
To explore the associations between periodontal status and incident MCI and dementia, the researchers studied participants in the ARIC study, a community-based longitudinal cohort consisting of 15,792 predominantly Black and White participants aged 45-64 years. The current analysis included 8,275 individuals (55% women; 21% black; mean age, 63 years) who at baseline did not meet criteria for dementia or MCI.
A full-mouth periodontal examination was conducted at baseline and participants were categorized according to the severity and extent of gingival inflammation and tooth attachment loss based on the Periodontal Profile Class (PPC) seven-category model. Potential confounding variables included age, race, education level, physical activity, smoking status, oral hygiene and access to care, plasma lipid levels, APOE genotype, body mass index, blood pressure, type 2 diabetes, and heart failure.
Based on PPC categorization, 22% of the patients had healthy gums, 12% had mild periodontal disease, 8% had a high gingival inflammation index, and 12% had posterior disease (with 6% having severe disease). In addition, 9% had tooth loss, 11% had severe tooth loss, and 20% were edentulous.
Infection hypothesis
Results showed that participants with worse periodontal status were more likely to have risk factors for vascular disease and dementia, such as smoking, hypertension, diabetes, and coronary heart disease. During median follow-up of 18.4 years, 19% of participants overall (n = 1,569) developed dementia, translating into 11.8 cases per 1,000 person-years. There were notable differences between the PPC categories in rates of incident dementia, with edentulous participants at twice the risk for developing dementia, compared with those who had healthy gums.
For participants with severe PPC, including severe tooth loss and severe disease, the multivariable-adjusted hazard ratio for incident dementia was 1.22 (95% confidence interval, 1.01-1.47) versus those who were periodontally healthy. For participants with edentulism, the HR was 1.21 (95% CI, 0.99-1.48). The adjusted risk ratios for the combined dementia/MCI outcome among participants with mild to intermediate PPC, severe PPC, or edentulism versus the periodontal healthy group were 1.22 (95% CI, 1.00-1.48), 1.15 (95% CI, 0.88-1.51), and 1.90 (95% CI, 1.40-2.58), respectively.
These findings were most pronounced among younger (median age at dental exam, younger than 62) versus older (62 years and older) participants (P = .02). Severe disease or total tooth loss were associated with an approximately 20% greater dementia incidence during the follow-up period, compared with healthy gums.
The investigators noted that the findings were “generally consistent” when considering the combined outcome of MCI and dementia. However, they noted that the association between edentulism and MCI was “markedly stronger,” with an approximate 100% increase in MCI or MCI plus dementia.
The association between periodontal disease and MCI or dementia “is rooted in the infection hypothesis, meaning adverse microbial exposures in the mucosal surfaces of the mouth, especially the subgingival space,” Dr. Demmer said. “One notion is that there could somehow be a direct infection of the brain with oral organisms, which posits that the oral organism could travel to the brain, colonize there, and cause damage that impairs cognition.”
Another possible mechanism is that chronic systemic inflammation in response to oral infections can eventually lead to vascular disease which, in turn, is a known risk factor for future dementia, he noted.
“Brush and floss”
Commenting on the research findings, James M. Noble, MD, associate professor of neurology, Taub Institute for Research on Alzheimer’s and the Aging Brain, Columbia University, New York, called the study “well characterized both by whole-mouth assessments and cognitive assessments performed in a standardized manner.” Moreover, “the study was sufficiently sized to allow for exploration of age and suggests that oral health may be a more important factor earlier in the course of aging, in late adulthood,” said Dr. Noble, who was not involved with the research.
The study also “makes an important contribution to this field through a rigorously followed cohort and robust design for both periodontal predictor and cognitive outcome assessments,” he said, noting that, “as always, the take-home message is ‘brush and floss.’
“Although we don’t know if treating periodontal disease can help treat dementia, this study suggests that we have to pay attention to good oral hygiene and make referrals to dentists when appropriate,” Dr. Demmer added.
The ARIC trial is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute. Dr. Demmer, the study coauthors, and Dr. Noble have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
especially in those with severe gum inflammation and edentulism, new research suggests.
Over a 20-year period, investigators prospectively followed more than 8,000 individuals aged around 63 years who did not have cognitive impairment or dementia at baseline, grouping them based on the extent and severity of their periodontal disease and number of lost teeth.
Results showed that 14% of participants with healthy gums and all their teeth at baseline developed dementia, compared with 18% of those with mild periodontal disease and 22% who had severe periodontal disease. The highest percentage (23%) of participants who developed dementia was found in those who were edentulous.
After accounting for comorbidities that might affect dementia risk, edentulous participants had a 20% higher risk for developing MCI or dementia, compared with the healthy group.
Because the study was observational, “we don’t have knowledge of causality so we cannot state that if you treat periodontal disease you can prevent or treat dementia,” said lead author Ryan T. Demmer, PhD, MPH, associate professor, division of epidemiology and community health, University of Minnesota, Minneapolis. However, “the take-home message from this paper is that it further supports the possibility that oral infections could be a risk factor for dementia.”
The study was published online July 29 in Neurology.
The ARIC trial
Prior studies have “described the interrelation of tooth loss or periodontal disease and cognitive outcomes, although many reports were cross-sectional or case-control … and often lacked robust confounder adjustment,” the investigators noted. Additionally, lack of longitudinal data impedes the “potential for baseline periodontal status to predict incident MCI.”
To explore the associations between periodontal status and incident MCI and dementia, the researchers studied participants in the ARIC study, a community-based longitudinal cohort consisting of 15,792 predominantly Black and White participants aged 45-64 years. The current analysis included 8,275 individuals (55% women; 21% black; mean age, 63 years) who at baseline did not meet criteria for dementia or MCI.
A full-mouth periodontal examination was conducted at baseline and participants were categorized according to the severity and extent of gingival inflammation and tooth attachment loss based on the Periodontal Profile Class (PPC) seven-category model. Potential confounding variables included age, race, education level, physical activity, smoking status, oral hygiene and access to care, plasma lipid levels, APOE genotype, body mass index, blood pressure, type 2 diabetes, and heart failure.
Based on PPC categorization, 22% of the patients had healthy gums, 12% had mild periodontal disease, 8% had a high gingival inflammation index, and 12% had posterior disease (with 6% having severe disease). In addition, 9% had tooth loss, 11% had severe tooth loss, and 20% were edentulous.
Infection hypothesis
Results showed that participants with worse periodontal status were more likely to have risk factors for vascular disease and dementia, such as smoking, hypertension, diabetes, and coronary heart disease. During median follow-up of 18.4 years, 19% of participants overall (n = 1,569) developed dementia, translating into 11.8 cases per 1,000 person-years. There were notable differences between the PPC categories in rates of incident dementia, with edentulous participants at twice the risk for developing dementia, compared with those who had healthy gums.
For participants with severe PPC, including severe tooth loss and severe disease, the multivariable-adjusted hazard ratio for incident dementia was 1.22 (95% confidence interval, 1.01-1.47) versus those who were periodontally healthy. For participants with edentulism, the HR was 1.21 (95% CI, 0.99-1.48). The adjusted risk ratios for the combined dementia/MCI outcome among participants with mild to intermediate PPC, severe PPC, or edentulism versus the periodontal healthy group were 1.22 (95% CI, 1.00-1.48), 1.15 (95% CI, 0.88-1.51), and 1.90 (95% CI, 1.40-2.58), respectively.
These findings were most pronounced among younger (median age at dental exam, younger than 62) versus older (62 years and older) participants (P = .02). Severe disease or total tooth loss were associated with an approximately 20% greater dementia incidence during the follow-up period, compared with healthy gums.
The investigators noted that the findings were “generally consistent” when considering the combined outcome of MCI and dementia. However, they noted that the association between edentulism and MCI was “markedly stronger,” with an approximate 100% increase in MCI or MCI plus dementia.
The association between periodontal disease and MCI or dementia “is rooted in the infection hypothesis, meaning adverse microbial exposures in the mucosal surfaces of the mouth, especially the subgingival space,” Dr. Demmer said. “One notion is that there could somehow be a direct infection of the brain with oral organisms, which posits that the oral organism could travel to the brain, colonize there, and cause damage that impairs cognition.”
Another possible mechanism is that chronic systemic inflammation in response to oral infections can eventually lead to vascular disease which, in turn, is a known risk factor for future dementia, he noted.
“Brush and floss”
Commenting on the research findings, James M. Noble, MD, associate professor of neurology, Taub Institute for Research on Alzheimer’s and the Aging Brain, Columbia University, New York, called the study “well characterized both by whole-mouth assessments and cognitive assessments performed in a standardized manner.” Moreover, “the study was sufficiently sized to allow for exploration of age and suggests that oral health may be a more important factor earlier in the course of aging, in late adulthood,” said Dr. Noble, who was not involved with the research.
The study also “makes an important contribution to this field through a rigorously followed cohort and robust design for both periodontal predictor and cognitive outcome assessments,” he said, noting that, “as always, the take-home message is ‘brush and floss.’
“Although we don’t know if treating periodontal disease can help treat dementia, this study suggests that we have to pay attention to good oral hygiene and make referrals to dentists when appropriate,” Dr. Demmer added.
The ARIC trial is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute. Dr. Demmer, the study coauthors, and Dr. Noble have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Managing acute pain in inpatients on OUD therapy
“This is something we’re going to see more frequently, and many of us already have,” Theresa E. Vettese, MD, said at HM20 Virtual, hosted by the Society of Hospital Medicine.
The drastic drop in prescriptions for opioid pain medications in the last several years hasn’t curtailed the current opioid epidemic. Instead, the epidemic has to a great extent morphed into expanded use of illicit heroin and fentanyl, noted Dr. Vettese, an internist, hospitalist, and palliative care physician at Emory University and Grady Memorial Hospital in Atlanta.
Mythbusting
Treatment of acute pain in hospitalized patients on opioid agonist therapy for opioid use disorder (OUD) is actually pretty straightforward once a few common myths have been dispelled, she said.
One of these myths –common among both physicians and patients in treatment for OUD – is that prescribing opioids for management of acute pain will place such patients at risk for OUD relapse.
“In fact, the data really strongly suggest this is not the case,” Dr. Vettese said. “It will not worsen addiction. But if we don’t aggressively treat these patients’ acute pain, it puts them at higher risk for bad outcomes.”
Another myth – this one not uncommon among hospital pharmacy departments – is that only physicians with a special certification can prescribe methadone for inpatients.
“The federal laws are clear: Any physician who has a DEA license can prescribe methadone in the hospital acute care setting, not only for pain management, but also for treatment of opioid withdrawal. You can’t prescribe it in the outpatient setting for opioid withdrawal – that has to be dispensed through a federally regulated methadone outpatient treatment program. But in the hospital, we can feel safe that we can do so. You may need to educate your pharmacist about this,” she said.
Hospitalists also can prescribe buprenorphine in the acute care inpatient setting, both for pain and treatment of opioid withdrawal, without need for a DEA waiver.
“It’s useful to get some skills in using buprenorphine in the inpatient setting. You don’t need an X waiver, but I encourage everyone to do the X-waiver training because it’s a terrific educational session. It’s 8 hours for physicians and well worth it,” Dr. Vettese noted.
By federal law the inpatient physician also can prescribe 3 days of buprenorphine at discharge to get the patient to an outpatient provider.
Misconceptions also abound about NSAIDs as a nonopioid component of acute pain management in hospitalized patients. They actually are extremely effective for the treatment of musculoskeletal, orthopedic, procedural, migraine, and some types of cancer pain. The number needed to treat (NNT) for postoperative pain relief for ibuprofen or celecoxib is 2.5, and when used in conjunction with acetaminophen at 325 mg every 4 hours, that NNT drops to 1.5, similar to the NNT of 1.7 for oxycodone at 15 mg. It should be noted, however, that the bar defining effective pain relief in randomized studies is set rather low: A 50% greater reduction in pain than achieved with placebo.
Many hospitalists would like to use NSAIDs more often, but they’re leery of the associated risks of GI bleeding, ischemic cardiovascular events, and worsening kidney function. Dr. Vettese offered several risk-mitigation strategies to increase the use of NSAIDs as opioid-sparing agents for acute pain management.
She has changed her own clinical practice with regard to using NSAIDs in patients with chronic kidney disease in response to a 2019 systematic review by investigators at the University of Ottawa.
“This was a game changer for me because in this review, low-dose NSAIDs were safe in that they didn’t significantly increase the risk of worsening kidney failure even in patients with stage 3 chronic kidney disease. So this has expanded my use of NSAIDs in this population through stage 3 CKD. With a creatinine clearance below 30, however, kidney failure worsened rapidly, so I don’t do it in patients with CKD stage 4,” Dr. Vettese said.
Gastroenterologists categorize patients as being at high risk of GI bleeding related to NSAID use if they have a history of a complicated ulcer or they have at least three of the following risk factors: Age above 65 years, history of an uncomplicated ulcer, being on high-dose NSAID therapy, or concurrent use of aspirin, glucocorticoids, or anticoagulants. Patients are considered at moderate risk if they have one or two of the risk factors, and low risk if they have none. Dr. Vettese said that, while NSAIDs clearly should be avoided in the high-risk group, moderate-risk patients are a different matter.
“Many avoid the use of NSAIDs with moderate risk, but I think we can expand their use if we use the right NSAID and we use protective strategies,” Dr. Vettese said.
Celecoxib is the safest drug in terms of upper GI bleeding risk, but ibuprofen is close. They are associated with a 2.2-fold increased risk of bleeding when compared with risk in patients not on an NSAID. Naproxen or indeomethacin use carries a fourfold to fivefold increased risk.
“Celecoxib with a proton pump inhibitor is safest, followed by celecoxib alone, followed by ibuprofen with a proton pump inhibitor. So I advocate using NSAIDs more frequently in people who are at moderate risk by using them with a PPI,” she said.
There is persuasive evidence of increased cardiovascular risk in association with even short-duration NSAIDs, as the drugs are utilized in the treatment of acute pain in hospitalized patients. That being said, Dr. Vettese believes hospitalists can use these drugs safely in more patients by following a thoughtful cardiovascular risk-mitigation strategy developed by Italian investigators.
Communicating about pain management
“Communication is always the key to effective pain management in every situation,” Dr. Vettese emphasized.
“I talk to the patient about the goals of effective pain management. I’ll discourage the use of the 1-10 pain scale, and instead, I’ll be honest about expectations, saying, ‘You have a problem that will cause acute pain, and it’s unlikely that I will be able to completely relieve your pain. The goal is to improve your function so that you can get up and go the bathroom by yourself, and so that you can sleep for a few hours. That’s how we’re going to measure the efficacy of our pain-management program.’ ”
She explains to the patient that she’ll be using nonopioid medications and nondrug therapies along with oral opioid pain medications, which are less risky than IV opioids. She offers reassurance that this treatment strategy won’t cause an OUD relapse. She lets the patient know up-front that the opioids will be tapered as the acute pain improves.
For the patient who comes into the hospital on buprenorphine for OUD, she immediately checks with the state prescription drug monitoring program to make sure everything is above board and there’s no indication of doctor shopping for prescriptions. For in-hospital acute pain, it’s safe and effective to continue the outpatient dose. On an outpatient basis, however, the drug is given once daily. On that dosing schedule both the euphoric effect as well as the analgesic effect are lost, so for acute pain management in the hospital it’s recommended to split the dose into twice- or thrice-daily doses to achieve an analgesic effect.
Oral NSAIDs are part of the treatment strategy whenever possible. For severe acute pain, Dr. Vettese will prescribe an immediate-release opioid having a high affinity to the mu opioid receptor, such as oral hydromorphone, on an as-needed basis. The drug has onset of effect in 30 minutes, peak effect in 1 hour, and a duration of effect of 4-6 hours, although she recommends going with 4 hours to provide adequate analgesia.
“These patients will require much higher doses than the patients who are opioid naive,” she advised.
For the patient with acute pain who is admitted while on methadone for OUD, it’s important to call the outpatient treatment program to verify the dosage.
“You can split the dose of methadone to try to get better analgesia, although I can tell you that patients who are treated with methadone for OUD frequently don’t want to do that. And if they don’t want to, then I don’t,” the hospitalist said.
As with the patient on buprenorphine for OUD, she’ll use additional oral immediate-release opioids as needed for acute severe pain in a patient on methadone for medication-assisted OUD treatment.
Dr. Vettese reported having no financial conflicts regarding her presentation.
“This is something we’re going to see more frequently, and many of us already have,” Theresa E. Vettese, MD, said at HM20 Virtual, hosted by the Society of Hospital Medicine.
The drastic drop in prescriptions for opioid pain medications in the last several years hasn’t curtailed the current opioid epidemic. Instead, the epidemic has to a great extent morphed into expanded use of illicit heroin and fentanyl, noted Dr. Vettese, an internist, hospitalist, and palliative care physician at Emory University and Grady Memorial Hospital in Atlanta.
Mythbusting
Treatment of acute pain in hospitalized patients on opioid agonist therapy for opioid use disorder (OUD) is actually pretty straightforward once a few common myths have been dispelled, she said.
One of these myths –common among both physicians and patients in treatment for OUD – is that prescribing opioids for management of acute pain will place such patients at risk for OUD relapse.
“In fact, the data really strongly suggest this is not the case,” Dr. Vettese said. “It will not worsen addiction. But if we don’t aggressively treat these patients’ acute pain, it puts them at higher risk for bad outcomes.”
Another myth – this one not uncommon among hospital pharmacy departments – is that only physicians with a special certification can prescribe methadone for inpatients.
“The federal laws are clear: Any physician who has a DEA license can prescribe methadone in the hospital acute care setting, not only for pain management, but also for treatment of opioid withdrawal. You can’t prescribe it in the outpatient setting for opioid withdrawal – that has to be dispensed through a federally regulated methadone outpatient treatment program. But in the hospital, we can feel safe that we can do so. You may need to educate your pharmacist about this,” she said.
Hospitalists also can prescribe buprenorphine in the acute care inpatient setting, both for pain and treatment of opioid withdrawal, without need for a DEA waiver.
“It’s useful to get some skills in using buprenorphine in the inpatient setting. You don’t need an X waiver, but I encourage everyone to do the X-waiver training because it’s a terrific educational session. It’s 8 hours for physicians and well worth it,” Dr. Vettese noted.
By federal law the inpatient physician also can prescribe 3 days of buprenorphine at discharge to get the patient to an outpatient provider.
Misconceptions also abound about NSAIDs as a nonopioid component of acute pain management in hospitalized patients. They actually are extremely effective for the treatment of musculoskeletal, orthopedic, procedural, migraine, and some types of cancer pain. The number needed to treat (NNT) for postoperative pain relief for ibuprofen or celecoxib is 2.5, and when used in conjunction with acetaminophen at 325 mg every 4 hours, that NNT drops to 1.5, similar to the NNT of 1.7 for oxycodone at 15 mg. It should be noted, however, that the bar defining effective pain relief in randomized studies is set rather low: A 50% greater reduction in pain than achieved with placebo.
Many hospitalists would like to use NSAIDs more often, but they’re leery of the associated risks of GI bleeding, ischemic cardiovascular events, and worsening kidney function. Dr. Vettese offered several risk-mitigation strategies to increase the use of NSAIDs as opioid-sparing agents for acute pain management.
She has changed her own clinical practice with regard to using NSAIDs in patients with chronic kidney disease in response to a 2019 systematic review by investigators at the University of Ottawa.
“This was a game changer for me because in this review, low-dose NSAIDs were safe in that they didn’t significantly increase the risk of worsening kidney failure even in patients with stage 3 chronic kidney disease. So this has expanded my use of NSAIDs in this population through stage 3 CKD. With a creatinine clearance below 30, however, kidney failure worsened rapidly, so I don’t do it in patients with CKD stage 4,” Dr. Vettese said.
Gastroenterologists categorize patients as being at high risk of GI bleeding related to NSAID use if they have a history of a complicated ulcer or they have at least three of the following risk factors: Age above 65 years, history of an uncomplicated ulcer, being on high-dose NSAID therapy, or concurrent use of aspirin, glucocorticoids, or anticoagulants. Patients are considered at moderate risk if they have one or two of the risk factors, and low risk if they have none. Dr. Vettese said that, while NSAIDs clearly should be avoided in the high-risk group, moderate-risk patients are a different matter.
“Many avoid the use of NSAIDs with moderate risk, but I think we can expand their use if we use the right NSAID and we use protective strategies,” Dr. Vettese said.
Celecoxib is the safest drug in terms of upper GI bleeding risk, but ibuprofen is close. They are associated with a 2.2-fold increased risk of bleeding when compared with risk in patients not on an NSAID. Naproxen or indeomethacin use carries a fourfold to fivefold increased risk.
“Celecoxib with a proton pump inhibitor is safest, followed by celecoxib alone, followed by ibuprofen with a proton pump inhibitor. So I advocate using NSAIDs more frequently in people who are at moderate risk by using them with a PPI,” she said.
There is persuasive evidence of increased cardiovascular risk in association with even short-duration NSAIDs, as the drugs are utilized in the treatment of acute pain in hospitalized patients. That being said, Dr. Vettese believes hospitalists can use these drugs safely in more patients by following a thoughtful cardiovascular risk-mitigation strategy developed by Italian investigators.
Communicating about pain management
“Communication is always the key to effective pain management in every situation,” Dr. Vettese emphasized.
“I talk to the patient about the goals of effective pain management. I’ll discourage the use of the 1-10 pain scale, and instead, I’ll be honest about expectations, saying, ‘You have a problem that will cause acute pain, and it’s unlikely that I will be able to completely relieve your pain. The goal is to improve your function so that you can get up and go the bathroom by yourself, and so that you can sleep for a few hours. That’s how we’re going to measure the efficacy of our pain-management program.’ ”
She explains to the patient that she’ll be using nonopioid medications and nondrug therapies along with oral opioid pain medications, which are less risky than IV opioids. She offers reassurance that this treatment strategy won’t cause an OUD relapse. She lets the patient know up-front that the opioids will be tapered as the acute pain improves.
For the patient who comes into the hospital on buprenorphine for OUD, she immediately checks with the state prescription drug monitoring program to make sure everything is above board and there’s no indication of doctor shopping for prescriptions. For in-hospital acute pain, it’s safe and effective to continue the outpatient dose. On an outpatient basis, however, the drug is given once daily. On that dosing schedule both the euphoric effect as well as the analgesic effect are lost, so for acute pain management in the hospital it’s recommended to split the dose into twice- or thrice-daily doses to achieve an analgesic effect.
Oral NSAIDs are part of the treatment strategy whenever possible. For severe acute pain, Dr. Vettese will prescribe an immediate-release opioid having a high affinity to the mu opioid receptor, such as oral hydromorphone, on an as-needed basis. The drug has onset of effect in 30 minutes, peak effect in 1 hour, and a duration of effect of 4-6 hours, although she recommends going with 4 hours to provide adequate analgesia.
“These patients will require much higher doses than the patients who are opioid naive,” she advised.
For the patient with acute pain who is admitted while on methadone for OUD, it’s important to call the outpatient treatment program to verify the dosage.
“You can split the dose of methadone to try to get better analgesia, although I can tell you that patients who are treated with methadone for OUD frequently don’t want to do that. And if they don’t want to, then I don’t,” the hospitalist said.
As with the patient on buprenorphine for OUD, she’ll use additional oral immediate-release opioids as needed for acute severe pain in a patient on methadone for medication-assisted OUD treatment.
Dr. Vettese reported having no financial conflicts regarding her presentation.
“This is something we’re going to see more frequently, and many of us already have,” Theresa E. Vettese, MD, said at HM20 Virtual, hosted by the Society of Hospital Medicine.
The drastic drop in prescriptions for opioid pain medications in the last several years hasn’t curtailed the current opioid epidemic. Instead, the epidemic has to a great extent morphed into expanded use of illicit heroin and fentanyl, noted Dr. Vettese, an internist, hospitalist, and palliative care physician at Emory University and Grady Memorial Hospital in Atlanta.
Mythbusting
Treatment of acute pain in hospitalized patients on opioid agonist therapy for opioid use disorder (OUD) is actually pretty straightforward once a few common myths have been dispelled, she said.
One of these myths –common among both physicians and patients in treatment for OUD – is that prescribing opioids for management of acute pain will place such patients at risk for OUD relapse.
“In fact, the data really strongly suggest this is not the case,” Dr. Vettese said. “It will not worsen addiction. But if we don’t aggressively treat these patients’ acute pain, it puts them at higher risk for bad outcomes.”
Another myth – this one not uncommon among hospital pharmacy departments – is that only physicians with a special certification can prescribe methadone for inpatients.
“The federal laws are clear: Any physician who has a DEA license can prescribe methadone in the hospital acute care setting, not only for pain management, but also for treatment of opioid withdrawal. You can’t prescribe it in the outpatient setting for opioid withdrawal – that has to be dispensed through a federally regulated methadone outpatient treatment program. But in the hospital, we can feel safe that we can do so. You may need to educate your pharmacist about this,” she said.
Hospitalists also can prescribe buprenorphine in the acute care inpatient setting, both for pain and treatment of opioid withdrawal, without need for a DEA waiver.
“It’s useful to get some skills in using buprenorphine in the inpatient setting. You don’t need an X waiver, but I encourage everyone to do the X-waiver training because it’s a terrific educational session. It’s 8 hours for physicians and well worth it,” Dr. Vettese noted.
By federal law the inpatient physician also can prescribe 3 days of buprenorphine at discharge to get the patient to an outpatient provider.
Misconceptions also abound about NSAIDs as a nonopioid component of acute pain management in hospitalized patients. They actually are extremely effective for the treatment of musculoskeletal, orthopedic, procedural, migraine, and some types of cancer pain. The number needed to treat (NNT) for postoperative pain relief for ibuprofen or celecoxib is 2.5, and when used in conjunction with acetaminophen at 325 mg every 4 hours, that NNT drops to 1.5, similar to the NNT of 1.7 for oxycodone at 15 mg. It should be noted, however, that the bar defining effective pain relief in randomized studies is set rather low: A 50% greater reduction in pain than achieved with placebo.
Many hospitalists would like to use NSAIDs more often, but they’re leery of the associated risks of GI bleeding, ischemic cardiovascular events, and worsening kidney function. Dr. Vettese offered several risk-mitigation strategies to increase the use of NSAIDs as opioid-sparing agents for acute pain management.
She has changed her own clinical practice with regard to using NSAIDs in patients with chronic kidney disease in response to a 2019 systematic review by investigators at the University of Ottawa.
“This was a game changer for me because in this review, low-dose NSAIDs were safe in that they didn’t significantly increase the risk of worsening kidney failure even in patients with stage 3 chronic kidney disease. So this has expanded my use of NSAIDs in this population through stage 3 CKD. With a creatinine clearance below 30, however, kidney failure worsened rapidly, so I don’t do it in patients with CKD stage 4,” Dr. Vettese said.
Gastroenterologists categorize patients as being at high risk of GI bleeding related to NSAID use if they have a history of a complicated ulcer or they have at least three of the following risk factors: Age above 65 years, history of an uncomplicated ulcer, being on high-dose NSAID therapy, or concurrent use of aspirin, glucocorticoids, or anticoagulants. Patients are considered at moderate risk if they have one or two of the risk factors, and low risk if they have none. Dr. Vettese said that, while NSAIDs clearly should be avoided in the high-risk group, moderate-risk patients are a different matter.
“Many avoid the use of NSAIDs with moderate risk, but I think we can expand their use if we use the right NSAID and we use protective strategies,” Dr. Vettese said.
Celecoxib is the safest drug in terms of upper GI bleeding risk, but ibuprofen is close. They are associated with a 2.2-fold increased risk of bleeding when compared with risk in patients not on an NSAID. Naproxen or indeomethacin use carries a fourfold to fivefold increased risk.
“Celecoxib with a proton pump inhibitor is safest, followed by celecoxib alone, followed by ibuprofen with a proton pump inhibitor. So I advocate using NSAIDs more frequently in people who are at moderate risk by using them with a PPI,” she said.
There is persuasive evidence of increased cardiovascular risk in association with even short-duration NSAIDs, as the drugs are utilized in the treatment of acute pain in hospitalized patients. That being said, Dr. Vettese believes hospitalists can use these drugs safely in more patients by following a thoughtful cardiovascular risk-mitigation strategy developed by Italian investigators.
Communicating about pain management
“Communication is always the key to effective pain management in every situation,” Dr. Vettese emphasized.
“I talk to the patient about the goals of effective pain management. I’ll discourage the use of the 1-10 pain scale, and instead, I’ll be honest about expectations, saying, ‘You have a problem that will cause acute pain, and it’s unlikely that I will be able to completely relieve your pain. The goal is to improve your function so that you can get up and go the bathroom by yourself, and so that you can sleep for a few hours. That’s how we’re going to measure the efficacy of our pain-management program.’ ”
She explains to the patient that she’ll be using nonopioid medications and nondrug therapies along with oral opioid pain medications, which are less risky than IV opioids. She offers reassurance that this treatment strategy won’t cause an OUD relapse. She lets the patient know up-front that the opioids will be tapered as the acute pain improves.
For the patient who comes into the hospital on buprenorphine for OUD, she immediately checks with the state prescription drug monitoring program to make sure everything is above board and there’s no indication of doctor shopping for prescriptions. For in-hospital acute pain, it’s safe and effective to continue the outpatient dose. On an outpatient basis, however, the drug is given once daily. On that dosing schedule both the euphoric effect as well as the analgesic effect are lost, so for acute pain management in the hospital it’s recommended to split the dose into twice- or thrice-daily doses to achieve an analgesic effect.
Oral NSAIDs are part of the treatment strategy whenever possible. For severe acute pain, Dr. Vettese will prescribe an immediate-release opioid having a high affinity to the mu opioid receptor, such as oral hydromorphone, on an as-needed basis. The drug has onset of effect in 30 minutes, peak effect in 1 hour, and a duration of effect of 4-6 hours, although she recommends going with 4 hours to provide adequate analgesia.
“These patients will require much higher doses than the patients who are opioid naive,” she advised.
For the patient with acute pain who is admitted while on methadone for OUD, it’s important to call the outpatient treatment program to verify the dosage.
“You can split the dose of methadone to try to get better analgesia, although I can tell you that patients who are treated with methadone for OUD frequently don’t want to do that. And if they don’t want to, then I don’t,” the hospitalist said.
As with the patient on buprenorphine for OUD, she’ll use additional oral immediate-release opioids as needed for acute severe pain in a patient on methadone for medication-assisted OUD treatment.
Dr. Vettese reported having no financial conflicts regarding her presentation.
FROM HM20 VIRTUAL
FDA approves ofatumumab (Kesimpta) for relapsing forms of MS
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
Are aging physicians a burden?
The evaluation of physicians with alleged cognitive decline
As forensic evaluators, we are often asked to review and assess the cognition of aging colleagues. The premise often involves a minor mistake, a poor choice of words, or a lapse in judgment. A physician gets reported for having difficulty using a new electronic form, forgetting the dose of a brand new medication, or getting upset in a public setting. Those behaviors often lead to mandatory psychiatric evaluations. Those requirements are often perceived by the provider as an insult, and betrayal by peers despite many years of dedicated work.
Interestingly, we have noticed many independent evaluators and hospital administrators using this opportunity to send many of our colleagues to pasture. There seems to be an unspoken rule among some forensic evaluators that physicians should represent some form of apex of humanity, beyond reproach, and beyond any fault. Those evaluators will point to any mistake on cognitive scales as proof that the aging physician is no longer safe to practice.1 Forgetting that Jill is from Illinois in the Saint Louis University Mental Status Examination test or how to copy a three-dimensional cube on the Montreal Cognitive Assessment can cost someone their license.2 We are also aware of some evaluators even taking the step further and opining that physicians not only need to score adequately but also demonstrate cognition significantly above average to maintain their privileges.
There is certainly significant appeal in setting a high bar for physicians. In many ways, physicians are characterized in society by their astuteness, intelligence, and high ethical standards. Patients place their lives in the hands of physicians and should trust that those physicians have the cognitive tools to heal them. It could almost seem evident that physicians should have high IQs, score perfectly on screening tools for dementia, and complete a mandatory psychiatric evaluation without any reproach. Yet the reality is often more complex.
We have two main concerns about the idea that we should be intransigent with aging physicians. The first one is the vast differential diagnosis for minor mistakes. An aging physician refusing to comply with a new form or yelling at a clerk once when asked to learn a new electronic medical record are inappropriate though not specific assessments for dementia. Similarly, having significant difficulty learning a new electronic medical record system more often is a sign of ageism rather than cognitive impairment. Subsequently, when arriving for their evaluation, forgetting the date is a common sign of anxiety. A relatable analogy would be to compare the mistake with a medical student forgetting part of the anatomy while questioning by an attending during surgery. Imagine such medical students being referred to mandatory psychiatric evaluation when failing to answer a question during rounds.
In our practice, the most common reason for those minor mistakes during our clinical evaluation is anxiety. After all, patients who present for problems completely unrelated to cognitive decline make similar mistakes. Psychological stressors in physicians require no introduction. The concept is so prevalent and pervasive that it has its own name, “burnout.” Imagine having dedicated most of one’s life to a profession then being enumerated a list of complaints, having one’s privileges put on hold, then being told to complete an independent psychiatric evaluation. If burnout is in part caused by a lack of control, unclear job expectations, rapidly changing models of health care, and dysfunctional workplace dynamics, imagine the consequence of such a referral.
The militant evaluator will use jargon to vilify the reviewed physician. If the physician complains too voraciously, he will be described as having signs of frontotemporal dementia. If the physician comes with a written list of rebuttals, he will be described as having memory problems requiring aids. If the physician is demoralized and quiet, he will be described as being withdrawn and apathetic. If the physician refuses to use or has difficulty with new forms or electronic systems, he will be described as having “impaired executive function,” an ominous term that surely should not be associated with a practicing physician.
The second concern arises from problems with the validity and use of diagnoses like mild cognitive impairment (MCI). MCI is considered to be a transition stage when one maintains “normal activities of daily living, and normal general cognitive function.”3 The American Psychiatric Association Textbook of Psychiatry mentions that there are “however, many cases of nonprogressive MCI.” Should a disorder with generally normal cognition and unclear progression to a more severe disorder require one to be dispensed of their privileges? Should any disorder trump an assessment of functioning?
It is our experience that many if not most physicians’ practice of medicine is not a job but a profession that defines who they are. As such, their occupational habits are an overly repeated and ingrained series of maneuvers analogous to so-called muscle memory. This kind of ritualistic pattern is precisely the kind of cognition that may persist as one starts to have some deficits. This requires the evaluator to be particularly sensitive and cognizant that one may still be able to perform professionally despite some mild but notable deficits. While it is facile to diagnose someone with MCI and justify removing their license, a review of their actual clinical skills is, despite being more time consuming, more pertinent to the evaluation.
In practice, we find that many cases lie in a gray area, which is hard to define. Physicians may come to our office for an evaluation after having said something odd at work. Maybe they misdosed a medication on one occasion. Maybe they wrote the wrong year on a chart. However, if the physician was 30 years old, would we consider any one of those incidents significant? As a psychiatrist rather than a physician practicing the specialty in review, it is particularly hard and sometimes unwise to condone or sanction individual incidents.
Evaluators find solace in neuropsychological testing. However the relevance to the safety of patients is unclear. Many of those tests end up being a simple proxy for age. A physicians’ ability to sort words or cards at a certain speed might correlate to cognitive performance but has unclear significance to the ability to care for patients. Using such tests becomes a de facto age limit on the practice of medicine. It seems essential to expand and refine our repertoire of evaluation tools for the assessment of physicians. As when we perform capacity evaluation in the hospital, we enlist the assistance of the treating team in understanding the questions being asked for a patient, medical boards could consider creating independent multidisciplinary teams where psychiatry has a seat along with the relevant specialties of the evaluee. Likewise, the assessment would benefit from a broad review of the physicians’ general practice rather than the more typical review of one or two incidents.
We are promoting a more individualized approach by medical boards to the many issues of the aging physician. Retiring is no longer the dream of older physicians, but rather working in the suitable position where their contributions, clinical experience, and wisdom are positive contributions to patient care. Furthermore, we encourage medical boards to consider more nuanced decisions. A binary approach fits few cases that we see. Surgeons are a prime example of this. A surgeon in the early stages of Parkinsonism may be unfit to perform surgery but very capable of continuing to contribute to the well-being of patients in other forms of clinical work, including postsurgical care that doesn’t involve physical dexterity. Similarly, medical boards could consider other forms of partial restrictions, including a ban on procedures, a ban on hospital privileges, as well as required supervision or working in teams. Accumulated clinical wisdom allows older physicians to be excellent mentors and educators for younger doctors. There is no simple method to predict which physicians may have the early stages of a progressive dementia, and which may have a stable MCI. A yearly reevaluation if there are no further complaints, is the best approach to determine progression of cognitive problems.
Few crises like the current COVID-19 pandemic can better remind us of the importance of the place of medicine in society. Many states have encouraged retired physicians to contribute their knowledge and expertise, putting themselves in particular risk because of their age. It is a good time to be reminded that we owe them significant respect and care when deciding to remove their license. We are encouraged by the diligent efforts of medical boards in supervising our colleagues but warn against zealot evaluators who use this opportunity to force physicians into retirement. We also encourage medical boards to expand their tools and approaches when facing such cases, as mislabeled cognitive diagnoses can be an easy scapegoat of a poor understanding of the more important psychological and biological factors in the evaluation.
References
1. Tariq SH et al. Am J Geriatr Psychiatry. 2006;14:900-10.
2. Nasreddine Z. mocatest.org. Version 2004 Nov 7.
3. Hales RE et al. The American Psychiatric Publishing Textbook of Psychiatry. Washington: American Psychiatric Association Publishing, 2014.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings in chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019). He has no disclosures.
Dr. Abrams is a forensic psychiatrist and attorney in San Diego. He is an expert in addictionology, behavioral toxicology, psychopharmacology and correctional mental health. He holds a teaching positions at the University of California, San Diego. Among his writings are chapters about competency in national textbooks. Dr. Abrams has no disclosures.
The evaluation of physicians with alleged cognitive decline
The evaluation of physicians with alleged cognitive decline
As forensic evaluators, we are often asked to review and assess the cognition of aging colleagues. The premise often involves a minor mistake, a poor choice of words, or a lapse in judgment. A physician gets reported for having difficulty using a new electronic form, forgetting the dose of a brand new medication, or getting upset in a public setting. Those behaviors often lead to mandatory psychiatric evaluations. Those requirements are often perceived by the provider as an insult, and betrayal by peers despite many years of dedicated work.
Interestingly, we have noticed many independent evaluators and hospital administrators using this opportunity to send many of our colleagues to pasture. There seems to be an unspoken rule among some forensic evaluators that physicians should represent some form of apex of humanity, beyond reproach, and beyond any fault. Those evaluators will point to any mistake on cognitive scales as proof that the aging physician is no longer safe to practice.1 Forgetting that Jill is from Illinois in the Saint Louis University Mental Status Examination test or how to copy a three-dimensional cube on the Montreal Cognitive Assessment can cost someone their license.2 We are also aware of some evaluators even taking the step further and opining that physicians not only need to score adequately but also demonstrate cognition significantly above average to maintain their privileges.
There is certainly significant appeal in setting a high bar for physicians. In many ways, physicians are characterized in society by their astuteness, intelligence, and high ethical standards. Patients place their lives in the hands of physicians and should trust that those physicians have the cognitive tools to heal them. It could almost seem evident that physicians should have high IQs, score perfectly on screening tools for dementia, and complete a mandatory psychiatric evaluation without any reproach. Yet the reality is often more complex.
We have two main concerns about the idea that we should be intransigent with aging physicians. The first one is the vast differential diagnosis for minor mistakes. An aging physician refusing to comply with a new form or yelling at a clerk once when asked to learn a new electronic medical record are inappropriate though not specific assessments for dementia. Similarly, having significant difficulty learning a new electronic medical record system more often is a sign of ageism rather than cognitive impairment. Subsequently, when arriving for their evaluation, forgetting the date is a common sign of anxiety. A relatable analogy would be to compare the mistake with a medical student forgetting part of the anatomy while questioning by an attending during surgery. Imagine such medical students being referred to mandatory psychiatric evaluation when failing to answer a question during rounds.
In our practice, the most common reason for those minor mistakes during our clinical evaluation is anxiety. After all, patients who present for problems completely unrelated to cognitive decline make similar mistakes. Psychological stressors in physicians require no introduction. The concept is so prevalent and pervasive that it has its own name, “burnout.” Imagine having dedicated most of one’s life to a profession then being enumerated a list of complaints, having one’s privileges put on hold, then being told to complete an independent psychiatric evaluation. If burnout is in part caused by a lack of control, unclear job expectations, rapidly changing models of health care, and dysfunctional workplace dynamics, imagine the consequence of such a referral.
The militant evaluator will use jargon to vilify the reviewed physician. If the physician complains too voraciously, he will be described as having signs of frontotemporal dementia. If the physician comes with a written list of rebuttals, he will be described as having memory problems requiring aids. If the physician is demoralized and quiet, he will be described as being withdrawn and apathetic. If the physician refuses to use or has difficulty with new forms or electronic systems, he will be described as having “impaired executive function,” an ominous term that surely should not be associated with a practicing physician.
The second concern arises from problems with the validity and use of diagnoses like mild cognitive impairment (MCI). MCI is considered to be a transition stage when one maintains “normal activities of daily living, and normal general cognitive function.”3 The American Psychiatric Association Textbook of Psychiatry mentions that there are “however, many cases of nonprogressive MCI.” Should a disorder with generally normal cognition and unclear progression to a more severe disorder require one to be dispensed of their privileges? Should any disorder trump an assessment of functioning?
It is our experience that many if not most physicians’ practice of medicine is not a job but a profession that defines who they are. As such, their occupational habits are an overly repeated and ingrained series of maneuvers analogous to so-called muscle memory. This kind of ritualistic pattern is precisely the kind of cognition that may persist as one starts to have some deficits. This requires the evaluator to be particularly sensitive and cognizant that one may still be able to perform professionally despite some mild but notable deficits. While it is facile to diagnose someone with MCI and justify removing their license, a review of their actual clinical skills is, despite being more time consuming, more pertinent to the evaluation.
In practice, we find that many cases lie in a gray area, which is hard to define. Physicians may come to our office for an evaluation after having said something odd at work. Maybe they misdosed a medication on one occasion. Maybe they wrote the wrong year on a chart. However, if the physician was 30 years old, would we consider any one of those incidents significant? As a psychiatrist rather than a physician practicing the specialty in review, it is particularly hard and sometimes unwise to condone or sanction individual incidents.
Evaluators find solace in neuropsychological testing. However the relevance to the safety of patients is unclear. Many of those tests end up being a simple proxy for age. A physicians’ ability to sort words or cards at a certain speed might correlate to cognitive performance but has unclear significance to the ability to care for patients. Using such tests becomes a de facto age limit on the practice of medicine. It seems essential to expand and refine our repertoire of evaluation tools for the assessment of physicians. As when we perform capacity evaluation in the hospital, we enlist the assistance of the treating team in understanding the questions being asked for a patient, medical boards could consider creating independent multidisciplinary teams where psychiatry has a seat along with the relevant specialties of the evaluee. Likewise, the assessment would benefit from a broad review of the physicians’ general practice rather than the more typical review of one or two incidents.
We are promoting a more individualized approach by medical boards to the many issues of the aging physician. Retiring is no longer the dream of older physicians, but rather working in the suitable position where their contributions, clinical experience, and wisdom are positive contributions to patient care. Furthermore, we encourage medical boards to consider more nuanced decisions. A binary approach fits few cases that we see. Surgeons are a prime example of this. A surgeon in the early stages of Parkinsonism may be unfit to perform surgery but very capable of continuing to contribute to the well-being of patients in other forms of clinical work, including postsurgical care that doesn’t involve physical dexterity. Similarly, medical boards could consider other forms of partial restrictions, including a ban on procedures, a ban on hospital privileges, as well as required supervision or working in teams. Accumulated clinical wisdom allows older physicians to be excellent mentors and educators for younger doctors. There is no simple method to predict which physicians may have the early stages of a progressive dementia, and which may have a stable MCI. A yearly reevaluation if there are no further complaints, is the best approach to determine progression of cognitive problems.
Few crises like the current COVID-19 pandemic can better remind us of the importance of the place of medicine in society. Many states have encouraged retired physicians to contribute their knowledge and expertise, putting themselves in particular risk because of their age. It is a good time to be reminded that we owe them significant respect and care when deciding to remove their license. We are encouraged by the diligent efforts of medical boards in supervising our colleagues but warn against zealot evaluators who use this opportunity to force physicians into retirement. We also encourage medical boards to expand their tools and approaches when facing such cases, as mislabeled cognitive diagnoses can be an easy scapegoat of a poor understanding of the more important psychological and biological factors in the evaluation.
References
1. Tariq SH et al. Am J Geriatr Psychiatry. 2006;14:900-10.
2. Nasreddine Z. mocatest.org. Version 2004 Nov 7.
3. Hales RE et al. The American Psychiatric Publishing Textbook of Psychiatry. Washington: American Psychiatric Association Publishing, 2014.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings in chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019). He has no disclosures.
Dr. Abrams is a forensic psychiatrist and attorney in San Diego. He is an expert in addictionology, behavioral toxicology, psychopharmacology and correctional mental health. He holds a teaching positions at the University of California, San Diego. Among his writings are chapters about competency in national textbooks. Dr. Abrams has no disclosures.
As forensic evaluators, we are often asked to review and assess the cognition of aging colleagues. The premise often involves a minor mistake, a poor choice of words, or a lapse in judgment. A physician gets reported for having difficulty using a new electronic form, forgetting the dose of a brand new medication, or getting upset in a public setting. Those behaviors often lead to mandatory psychiatric evaluations. Those requirements are often perceived by the provider as an insult, and betrayal by peers despite many years of dedicated work.
Interestingly, we have noticed many independent evaluators and hospital administrators using this opportunity to send many of our colleagues to pasture. There seems to be an unspoken rule among some forensic evaluators that physicians should represent some form of apex of humanity, beyond reproach, and beyond any fault. Those evaluators will point to any mistake on cognitive scales as proof that the aging physician is no longer safe to practice.1 Forgetting that Jill is from Illinois in the Saint Louis University Mental Status Examination test or how to copy a three-dimensional cube on the Montreal Cognitive Assessment can cost someone their license.2 We are also aware of some evaluators even taking the step further and opining that physicians not only need to score adequately but also demonstrate cognition significantly above average to maintain their privileges.
There is certainly significant appeal in setting a high bar for physicians. In many ways, physicians are characterized in society by their astuteness, intelligence, and high ethical standards. Patients place their lives in the hands of physicians and should trust that those physicians have the cognitive tools to heal them. It could almost seem evident that physicians should have high IQs, score perfectly on screening tools for dementia, and complete a mandatory psychiatric evaluation without any reproach. Yet the reality is often more complex.
We have two main concerns about the idea that we should be intransigent with aging physicians. The first one is the vast differential diagnosis for minor mistakes. An aging physician refusing to comply with a new form or yelling at a clerk once when asked to learn a new electronic medical record are inappropriate though not specific assessments for dementia. Similarly, having significant difficulty learning a new electronic medical record system more often is a sign of ageism rather than cognitive impairment. Subsequently, when arriving for their evaluation, forgetting the date is a common sign of anxiety. A relatable analogy would be to compare the mistake with a medical student forgetting part of the anatomy while questioning by an attending during surgery. Imagine such medical students being referred to mandatory psychiatric evaluation when failing to answer a question during rounds.
In our practice, the most common reason for those minor mistakes during our clinical evaluation is anxiety. After all, patients who present for problems completely unrelated to cognitive decline make similar mistakes. Psychological stressors in physicians require no introduction. The concept is so prevalent and pervasive that it has its own name, “burnout.” Imagine having dedicated most of one’s life to a profession then being enumerated a list of complaints, having one’s privileges put on hold, then being told to complete an independent psychiatric evaluation. If burnout is in part caused by a lack of control, unclear job expectations, rapidly changing models of health care, and dysfunctional workplace dynamics, imagine the consequence of such a referral.
The militant evaluator will use jargon to vilify the reviewed physician. If the physician complains too voraciously, he will be described as having signs of frontotemporal dementia. If the physician comes with a written list of rebuttals, he will be described as having memory problems requiring aids. If the physician is demoralized and quiet, he will be described as being withdrawn and apathetic. If the physician refuses to use or has difficulty with new forms or electronic systems, he will be described as having “impaired executive function,” an ominous term that surely should not be associated with a practicing physician.
The second concern arises from problems with the validity and use of diagnoses like mild cognitive impairment (MCI). MCI is considered to be a transition stage when one maintains “normal activities of daily living, and normal general cognitive function.”3 The American Psychiatric Association Textbook of Psychiatry mentions that there are “however, many cases of nonprogressive MCI.” Should a disorder with generally normal cognition and unclear progression to a more severe disorder require one to be dispensed of their privileges? Should any disorder trump an assessment of functioning?
It is our experience that many if not most physicians’ practice of medicine is not a job but a profession that defines who they are. As such, their occupational habits are an overly repeated and ingrained series of maneuvers analogous to so-called muscle memory. This kind of ritualistic pattern is precisely the kind of cognition that may persist as one starts to have some deficits. This requires the evaluator to be particularly sensitive and cognizant that one may still be able to perform professionally despite some mild but notable deficits. While it is facile to diagnose someone with MCI and justify removing their license, a review of their actual clinical skills is, despite being more time consuming, more pertinent to the evaluation.
In practice, we find that many cases lie in a gray area, which is hard to define. Physicians may come to our office for an evaluation after having said something odd at work. Maybe they misdosed a medication on one occasion. Maybe they wrote the wrong year on a chart. However, if the physician was 30 years old, would we consider any one of those incidents significant? As a psychiatrist rather than a physician practicing the specialty in review, it is particularly hard and sometimes unwise to condone or sanction individual incidents.
Evaluators find solace in neuropsychological testing. However the relevance to the safety of patients is unclear. Many of those tests end up being a simple proxy for age. A physicians’ ability to sort words or cards at a certain speed might correlate to cognitive performance but has unclear significance to the ability to care for patients. Using such tests becomes a de facto age limit on the practice of medicine. It seems essential to expand and refine our repertoire of evaluation tools for the assessment of physicians. As when we perform capacity evaluation in the hospital, we enlist the assistance of the treating team in understanding the questions being asked for a patient, medical boards could consider creating independent multidisciplinary teams where psychiatry has a seat along with the relevant specialties of the evaluee. Likewise, the assessment would benefit from a broad review of the physicians’ general practice rather than the more typical review of one or two incidents.
We are promoting a more individualized approach by medical boards to the many issues of the aging physician. Retiring is no longer the dream of older physicians, but rather working in the suitable position where their contributions, clinical experience, and wisdom are positive contributions to patient care. Furthermore, we encourage medical boards to consider more nuanced decisions. A binary approach fits few cases that we see. Surgeons are a prime example of this. A surgeon in the early stages of Parkinsonism may be unfit to perform surgery but very capable of continuing to contribute to the well-being of patients in other forms of clinical work, including postsurgical care that doesn’t involve physical dexterity. Similarly, medical boards could consider other forms of partial restrictions, including a ban on procedures, a ban on hospital privileges, as well as required supervision or working in teams. Accumulated clinical wisdom allows older physicians to be excellent mentors and educators for younger doctors. There is no simple method to predict which physicians may have the early stages of a progressive dementia, and which may have a stable MCI. A yearly reevaluation if there are no further complaints, is the best approach to determine progression of cognitive problems.
Few crises like the current COVID-19 pandemic can better remind us of the importance of the place of medicine in society. Many states have encouraged retired physicians to contribute their knowledge and expertise, putting themselves in particular risk because of their age. It is a good time to be reminded that we owe them significant respect and care when deciding to remove their license. We are encouraged by the diligent efforts of medical boards in supervising our colleagues but warn against zealot evaluators who use this opportunity to force physicians into retirement. We also encourage medical boards to expand their tools and approaches when facing such cases, as mislabeled cognitive diagnoses can be an easy scapegoat of a poor understanding of the more important psychological and biological factors in the evaluation.
References
1. Tariq SH et al. Am J Geriatr Psychiatry. 2006;14:900-10.
2. Nasreddine Z. mocatest.org. Version 2004 Nov 7.
3. Hales RE et al. The American Psychiatric Publishing Textbook of Psychiatry. Washington: American Psychiatric Association Publishing, 2014.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings in chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019). He has no disclosures.
Dr. Abrams is a forensic psychiatrist and attorney in San Diego. He is an expert in addictionology, behavioral toxicology, psychopharmacology and correctional mental health. He holds a teaching positions at the University of California, San Diego. Among his writings are chapters about competency in national textbooks. Dr. Abrams has no disclosures.
Impaired senses, especially smell, linked to dementia
new research suggests. The study, which included almost 1,800 participants, adds to emerging evidence that even mild levels of multisensory impairment are associated with accelerated cognitive aging, the researchers noted.
Clinicians should be aware of this link between sensory impairment and dementia risk, said lead author Willa Brenowitz, PhD, assistant professor, department of psychiatry and behavioral sciences, University of California, San Francisco. “Many of these impairments are treatable, or at least physicians can monitor them; and this can improve quality of life, even if it doesn’t improve dementia risk.”
The findings were published online July 12 in Alzheimer’s and Dementia.
Additive effects
Previous research has focused on the link between dementia and individual senses, but this new work is unique in that it focuses on the additive effects of multiple impairments in sensory function, said Dr. Brenowitz. The study included 1,794 dementia-free participants in their 70s from the Health, Aging and Body Composition study, a prospective cohort study of healthy Black and White men and women.
Researchers tested participants’ hearing using a pure tone average without hearing aids and vision using contrast sensitivity with glasses permitted. They also measured vibrations in the big toe to assess touch and had participants identify distinctive odors such as paint thinner, roses, lemons, and onions to assess smell.
A score of 0-3 was assigned based on sample quartiles for each of the four sensory functions. Individuals with the best quartile were assigned a score of 0 and those with the worst were assigned a score of 3.
The investigators added scores across all senses to create a summary score of multisensory function (0-12) and classified the participants into tertiles of good, medium, and poor. Individuals with a score of 0 would have good function in all senses, whereas those with 12 would have poor function in all senses. Those with medium scores could have a mix of impairments.
Participants with good multisensory function were more likely to be healthier than those with poor function. They were also significantly more likely to have completed high school (85.0% vs. 72.1%), were significantly less likely to have diabetes (16.9% vs. 27.9%), and were marginally less likely to have cardiovascular disease, high blood pressure, and history of stroke.
Investigators measured cognition using the Modified Mini-Mental State (3MS) examination, a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a measure of cognitive processing speed. Cognitive testing was carried out at the beginning of the study and repeated every other year.
Dementia was defined as the use of dementia medication, being hospitalized with dementia as a primary or secondary diagnosis, or having a 3MS score 1.5 standard deviations lower than the race-stratified Health ABC study baseline mean.
Over an average follow-up of 6.3 years, 18% of participants developed dementia.
Dose-response increase
Results showed that, with worsening multisensory function score, the risk for dementia increased in a dose-response manner. In models adjusted for demographics and health conditions, participants with a poor multisensory function score were more than twice as likely to develop dementia than those with a good score (hazard ratio, 2.05; 95% confidence interval, 1.50-2.81; P < .001). Those with a middle multisensory function score were 1.45 times more likely to develop dementia (HR, 1.45; 95% CI, 1.09-1.91; P < .001).
Even a 1-point worse multisensory function score was associated with a 14% higher risk for dementia (95% CI, 8%-21%), while a 4-point worse score was associated with 71% higher risk for dementia (95% CI, 38%-211%).
Smell was the sensory function most strongly associated with dementia risk. Participants whose sense of smell declined by 10% had a 19% higher risk for dementia versus a 1%-3% higher risk for declines in vision, hearing, and touch.
It is not clear why smell was a stronger determinant of dementia risk. However, loss of this sense is often considered to be a marker for Alzheimer’s disease “because it is closely linked with brain regions that are affected” in that disease, said Dr. Brenowitz.
However, that does not necessarily mean smell is more important than vision or hearing, she added. “Even if hearing and vision have a smaller contribution to dementia, they have a stronger potential for intervention.” The findings suggest “some additive or cumulative” effects for loss of the different senses. “There’s an association above and beyond those which can be attributed to individual sensory domains,” she said.
Frailty link
After including mobility, which is a potential mediator, estimates for the multisensory function score were slightly lower. “Walking speed is pretty strongly associated with dementia risk,” Dr. Brenowitz noted. Physical frailty might help explain the link between sensory impairment and dementia risk. “It’s not clear if that’s because people with dementia are declining or because people with frailty are especially vulnerable to dementia,” she said.
The researchers also assessed the role of social support, another potential mechanism by which sensory decline, especially in hearing and vision, could influence dementia risk. Although the study did not find substantial differences in social support measures, the investigators noted that questions assessing social support were limited in scope.
Interactions between multisensory function score and race, APOE e4 allele status, and sex were not significant.
Worsening multisensory function was also linked to faster annual rates of cognitive decline as measured by both the 3MS and DSST. Each 1-point worse score was associated with faster decline (P < .05), even after adjustment for demographics and health conditions.
Possible mechanisms
A number of possible mechanisms may explain the link between poor sensory function and dementia. It could be that neurodegeneration underlying dementia affects the senses, or vision and/or hearing loss leads to social isolation and poor mental health, which in turn could affect dementia risk, the researchers wrote. It also is possible that cardiovascular disease or diabetes affect both dementia risk and sensory impairment.
Dr. Brenowitz noted that, because cognitive tests rely on a certain degree of vision and hearing, impairment of these senses may complicate such tests. Still to be determined is whether correcting sensory impairments, such as wearing corrective lenses or hearing aids, affects dementia risk.
Meanwhile, it might be a good idea to more regularly check sensory function, especially vision and hearing, the researchers suggested. These functions affect various aspects of health and can be assessed rather easily. However, because smell is so strongly associated with dementia risk, Dr. Brenowitz said she would like to see it also become “part of a screening tool.”
A possible study limitation cited was that the researchers checked sensory function only once. “Most likely, some of these would change over time, but at least it captured sensory function at one point,” Dr. Brenowitz said.
“Sheds further light”
Commenting on the study, Jo V. Rushworth, PhD, associate professor and national teaching fellow, De Montfort University Leicester (England), said it “sheds further light on the emerging links” between multisensory impairment and cognitive decline leading to dementia. “The authors show that people with even mild loss of function in various senses are more likely to develop cognitive impairment.”
Dr. Rushworth was not involved with the study but has done research in the area.
The current results suggest that measuring patients’ hearing, vision, sense of smell, and touch might “flag at-risk groups” who could be targeted for dementia prevention strategies, Dr. Rushworth noted. Such tests are noninvasive and potentially less distressing than other methods of diagnosing dementia. “Importantly, the relatively low cost and simplicity of sensory tests offer the potential for more frequent testing and the use of these methods in areas of the world where medical facilities and resources are limited.”
This new study raises the question of whether the observed sensory impairments are a cause or an effect of dementia, Dr. Rushworth noted. “As the authors suggest, decreased sensory function can lead to a decrease in social engagement, mobility, and other factors which would usually contribute to counteracting cognitive decline.”
The study raises other questions, too, said Dr. Rushworth. She noted that the participants who experienced more severe sensory impairments were, on average, 2 years older than those with the least impairments. “To what degree were the observed sensory deficits linked to normal aging rather than dementia?”
As well, Dr. Rushworth pointed out that the molecular mechanisms that “kick-start” dementia are believed to occur in midlife – so possibly at an age younger than the study participants. “Do younger people of a ‘predementia’ age range display multisensory impairments?”
Because study participants could wear glasses during vision tests but were not allowed to wear hearing aids for the hearing tests, further standardization of sensory impairment is required, Dr. Rushworth said.
“Future studies will be essential in determining the value of clinical measurement of multisensory impairment as a possible dementia indicator and prevention strategy,” she concluded.
The study was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Alzheimer’s Association. Dr. Brenowitz and Dr. Rushworth have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests. The study, which included almost 1,800 participants, adds to emerging evidence that even mild levels of multisensory impairment are associated with accelerated cognitive aging, the researchers noted.
Clinicians should be aware of this link between sensory impairment and dementia risk, said lead author Willa Brenowitz, PhD, assistant professor, department of psychiatry and behavioral sciences, University of California, San Francisco. “Many of these impairments are treatable, or at least physicians can monitor them; and this can improve quality of life, even if it doesn’t improve dementia risk.”
The findings were published online July 12 in Alzheimer’s and Dementia.
Additive effects
Previous research has focused on the link between dementia and individual senses, but this new work is unique in that it focuses on the additive effects of multiple impairments in sensory function, said Dr. Brenowitz. The study included 1,794 dementia-free participants in their 70s from the Health, Aging and Body Composition study, a prospective cohort study of healthy Black and White men and women.
Researchers tested participants’ hearing using a pure tone average without hearing aids and vision using contrast sensitivity with glasses permitted. They also measured vibrations in the big toe to assess touch and had participants identify distinctive odors such as paint thinner, roses, lemons, and onions to assess smell.
A score of 0-3 was assigned based on sample quartiles for each of the four sensory functions. Individuals with the best quartile were assigned a score of 0 and those with the worst were assigned a score of 3.
The investigators added scores across all senses to create a summary score of multisensory function (0-12) and classified the participants into tertiles of good, medium, and poor. Individuals with a score of 0 would have good function in all senses, whereas those with 12 would have poor function in all senses. Those with medium scores could have a mix of impairments.
Participants with good multisensory function were more likely to be healthier than those with poor function. They were also significantly more likely to have completed high school (85.0% vs. 72.1%), were significantly less likely to have diabetes (16.9% vs. 27.9%), and were marginally less likely to have cardiovascular disease, high blood pressure, and history of stroke.
Investigators measured cognition using the Modified Mini-Mental State (3MS) examination, a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a measure of cognitive processing speed. Cognitive testing was carried out at the beginning of the study and repeated every other year.
Dementia was defined as the use of dementia medication, being hospitalized with dementia as a primary or secondary diagnosis, or having a 3MS score 1.5 standard deviations lower than the race-stratified Health ABC study baseline mean.
Over an average follow-up of 6.3 years, 18% of participants developed dementia.
Dose-response increase
Results showed that, with worsening multisensory function score, the risk for dementia increased in a dose-response manner. In models adjusted for demographics and health conditions, participants with a poor multisensory function score were more than twice as likely to develop dementia than those with a good score (hazard ratio, 2.05; 95% confidence interval, 1.50-2.81; P < .001). Those with a middle multisensory function score were 1.45 times more likely to develop dementia (HR, 1.45; 95% CI, 1.09-1.91; P < .001).
Even a 1-point worse multisensory function score was associated with a 14% higher risk for dementia (95% CI, 8%-21%), while a 4-point worse score was associated with 71% higher risk for dementia (95% CI, 38%-211%).
Smell was the sensory function most strongly associated with dementia risk. Participants whose sense of smell declined by 10% had a 19% higher risk for dementia versus a 1%-3% higher risk for declines in vision, hearing, and touch.
It is not clear why smell was a stronger determinant of dementia risk. However, loss of this sense is often considered to be a marker for Alzheimer’s disease “because it is closely linked with brain regions that are affected” in that disease, said Dr. Brenowitz.
However, that does not necessarily mean smell is more important than vision or hearing, she added. “Even if hearing and vision have a smaller contribution to dementia, they have a stronger potential for intervention.” The findings suggest “some additive or cumulative” effects for loss of the different senses. “There’s an association above and beyond those which can be attributed to individual sensory domains,” she said.
Frailty link
After including mobility, which is a potential mediator, estimates for the multisensory function score were slightly lower. “Walking speed is pretty strongly associated with dementia risk,” Dr. Brenowitz noted. Physical frailty might help explain the link between sensory impairment and dementia risk. “It’s not clear if that’s because people with dementia are declining or because people with frailty are especially vulnerable to dementia,” she said.
The researchers also assessed the role of social support, another potential mechanism by which sensory decline, especially in hearing and vision, could influence dementia risk. Although the study did not find substantial differences in social support measures, the investigators noted that questions assessing social support were limited in scope.
Interactions between multisensory function score and race, APOE e4 allele status, and sex were not significant.
Worsening multisensory function was also linked to faster annual rates of cognitive decline as measured by both the 3MS and DSST. Each 1-point worse score was associated with faster decline (P < .05), even after adjustment for demographics and health conditions.
Possible mechanisms
A number of possible mechanisms may explain the link between poor sensory function and dementia. It could be that neurodegeneration underlying dementia affects the senses, or vision and/or hearing loss leads to social isolation and poor mental health, which in turn could affect dementia risk, the researchers wrote. It also is possible that cardiovascular disease or diabetes affect both dementia risk and sensory impairment.
Dr. Brenowitz noted that, because cognitive tests rely on a certain degree of vision and hearing, impairment of these senses may complicate such tests. Still to be determined is whether correcting sensory impairments, such as wearing corrective lenses or hearing aids, affects dementia risk.
Meanwhile, it might be a good idea to more regularly check sensory function, especially vision and hearing, the researchers suggested. These functions affect various aspects of health and can be assessed rather easily. However, because smell is so strongly associated with dementia risk, Dr. Brenowitz said she would like to see it also become “part of a screening tool.”
A possible study limitation cited was that the researchers checked sensory function only once. “Most likely, some of these would change over time, but at least it captured sensory function at one point,” Dr. Brenowitz said.
“Sheds further light”
Commenting on the study, Jo V. Rushworth, PhD, associate professor and national teaching fellow, De Montfort University Leicester (England), said it “sheds further light on the emerging links” between multisensory impairment and cognitive decline leading to dementia. “The authors show that people with even mild loss of function in various senses are more likely to develop cognitive impairment.”
Dr. Rushworth was not involved with the study but has done research in the area.
The current results suggest that measuring patients’ hearing, vision, sense of smell, and touch might “flag at-risk groups” who could be targeted for dementia prevention strategies, Dr. Rushworth noted. Such tests are noninvasive and potentially less distressing than other methods of diagnosing dementia. “Importantly, the relatively low cost and simplicity of sensory tests offer the potential for more frequent testing and the use of these methods in areas of the world where medical facilities and resources are limited.”
This new study raises the question of whether the observed sensory impairments are a cause or an effect of dementia, Dr. Rushworth noted. “As the authors suggest, decreased sensory function can lead to a decrease in social engagement, mobility, and other factors which would usually contribute to counteracting cognitive decline.”
The study raises other questions, too, said Dr. Rushworth. She noted that the participants who experienced more severe sensory impairments were, on average, 2 years older than those with the least impairments. “To what degree were the observed sensory deficits linked to normal aging rather than dementia?”
As well, Dr. Rushworth pointed out that the molecular mechanisms that “kick-start” dementia are believed to occur in midlife – so possibly at an age younger than the study participants. “Do younger people of a ‘predementia’ age range display multisensory impairments?”
Because study participants could wear glasses during vision tests but were not allowed to wear hearing aids for the hearing tests, further standardization of sensory impairment is required, Dr. Rushworth said.
“Future studies will be essential in determining the value of clinical measurement of multisensory impairment as a possible dementia indicator and prevention strategy,” she concluded.
The study was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Alzheimer’s Association. Dr. Brenowitz and Dr. Rushworth have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests. The study, which included almost 1,800 participants, adds to emerging evidence that even mild levels of multisensory impairment are associated with accelerated cognitive aging, the researchers noted.
Clinicians should be aware of this link between sensory impairment and dementia risk, said lead author Willa Brenowitz, PhD, assistant professor, department of psychiatry and behavioral sciences, University of California, San Francisco. “Many of these impairments are treatable, or at least physicians can monitor them; and this can improve quality of life, even if it doesn’t improve dementia risk.”
The findings were published online July 12 in Alzheimer’s and Dementia.
Additive effects
Previous research has focused on the link between dementia and individual senses, but this new work is unique in that it focuses on the additive effects of multiple impairments in sensory function, said Dr. Brenowitz. The study included 1,794 dementia-free participants in their 70s from the Health, Aging and Body Composition study, a prospective cohort study of healthy Black and White men and women.
Researchers tested participants’ hearing using a pure tone average without hearing aids and vision using contrast sensitivity with glasses permitted. They also measured vibrations in the big toe to assess touch and had participants identify distinctive odors such as paint thinner, roses, lemons, and onions to assess smell.
A score of 0-3 was assigned based on sample quartiles for each of the four sensory functions. Individuals with the best quartile were assigned a score of 0 and those with the worst were assigned a score of 3.
The investigators added scores across all senses to create a summary score of multisensory function (0-12) and classified the participants into tertiles of good, medium, and poor. Individuals with a score of 0 would have good function in all senses, whereas those with 12 would have poor function in all senses. Those with medium scores could have a mix of impairments.
Participants with good multisensory function were more likely to be healthier than those with poor function. They were also significantly more likely to have completed high school (85.0% vs. 72.1%), were significantly less likely to have diabetes (16.9% vs. 27.9%), and were marginally less likely to have cardiovascular disease, high blood pressure, and history of stroke.
Investigators measured cognition using the Modified Mini-Mental State (3MS) examination, a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a measure of cognitive processing speed. Cognitive testing was carried out at the beginning of the study and repeated every other year.
Dementia was defined as the use of dementia medication, being hospitalized with dementia as a primary or secondary diagnosis, or having a 3MS score 1.5 standard deviations lower than the race-stratified Health ABC study baseline mean.
Over an average follow-up of 6.3 years, 18% of participants developed dementia.
Dose-response increase
Results showed that, with worsening multisensory function score, the risk for dementia increased in a dose-response manner. In models adjusted for demographics and health conditions, participants with a poor multisensory function score were more than twice as likely to develop dementia than those with a good score (hazard ratio, 2.05; 95% confidence interval, 1.50-2.81; P < .001). Those with a middle multisensory function score were 1.45 times more likely to develop dementia (HR, 1.45; 95% CI, 1.09-1.91; P < .001).
Even a 1-point worse multisensory function score was associated with a 14% higher risk for dementia (95% CI, 8%-21%), while a 4-point worse score was associated with 71% higher risk for dementia (95% CI, 38%-211%).
Smell was the sensory function most strongly associated with dementia risk. Participants whose sense of smell declined by 10% had a 19% higher risk for dementia versus a 1%-3% higher risk for declines in vision, hearing, and touch.
It is not clear why smell was a stronger determinant of dementia risk. However, loss of this sense is often considered to be a marker for Alzheimer’s disease “because it is closely linked with brain regions that are affected” in that disease, said Dr. Brenowitz.
However, that does not necessarily mean smell is more important than vision or hearing, she added. “Even if hearing and vision have a smaller contribution to dementia, they have a stronger potential for intervention.” The findings suggest “some additive or cumulative” effects for loss of the different senses. “There’s an association above and beyond those which can be attributed to individual sensory domains,” she said.
Frailty link
After including mobility, which is a potential mediator, estimates for the multisensory function score were slightly lower. “Walking speed is pretty strongly associated with dementia risk,” Dr. Brenowitz noted. Physical frailty might help explain the link between sensory impairment and dementia risk. “It’s not clear if that’s because people with dementia are declining or because people with frailty are especially vulnerable to dementia,” she said.
The researchers also assessed the role of social support, another potential mechanism by which sensory decline, especially in hearing and vision, could influence dementia risk. Although the study did not find substantial differences in social support measures, the investigators noted that questions assessing social support were limited in scope.
Interactions between multisensory function score and race, APOE e4 allele status, and sex were not significant.
Worsening multisensory function was also linked to faster annual rates of cognitive decline as measured by both the 3MS and DSST. Each 1-point worse score was associated with faster decline (P < .05), even after adjustment for demographics and health conditions.
Possible mechanisms
A number of possible mechanisms may explain the link between poor sensory function and dementia. It could be that neurodegeneration underlying dementia affects the senses, or vision and/or hearing loss leads to social isolation and poor mental health, which in turn could affect dementia risk, the researchers wrote. It also is possible that cardiovascular disease or diabetes affect both dementia risk and sensory impairment.
Dr. Brenowitz noted that, because cognitive tests rely on a certain degree of vision and hearing, impairment of these senses may complicate such tests. Still to be determined is whether correcting sensory impairments, such as wearing corrective lenses or hearing aids, affects dementia risk.
Meanwhile, it might be a good idea to more regularly check sensory function, especially vision and hearing, the researchers suggested. These functions affect various aspects of health and can be assessed rather easily. However, because smell is so strongly associated with dementia risk, Dr. Brenowitz said she would like to see it also become “part of a screening tool.”
A possible study limitation cited was that the researchers checked sensory function only once. “Most likely, some of these would change over time, but at least it captured sensory function at one point,” Dr. Brenowitz said.
“Sheds further light”
Commenting on the study, Jo V. Rushworth, PhD, associate professor and national teaching fellow, De Montfort University Leicester (England), said it “sheds further light on the emerging links” between multisensory impairment and cognitive decline leading to dementia. “The authors show that people with even mild loss of function in various senses are more likely to develop cognitive impairment.”
Dr. Rushworth was not involved with the study but has done research in the area.
The current results suggest that measuring patients’ hearing, vision, sense of smell, and touch might “flag at-risk groups” who could be targeted for dementia prevention strategies, Dr. Rushworth noted. Such tests are noninvasive and potentially less distressing than other methods of diagnosing dementia. “Importantly, the relatively low cost and simplicity of sensory tests offer the potential for more frequent testing and the use of these methods in areas of the world where medical facilities and resources are limited.”
This new study raises the question of whether the observed sensory impairments are a cause or an effect of dementia, Dr. Rushworth noted. “As the authors suggest, decreased sensory function can lead to a decrease in social engagement, mobility, and other factors which would usually contribute to counteracting cognitive decline.”
The study raises other questions, too, said Dr. Rushworth. She noted that the participants who experienced more severe sensory impairments were, on average, 2 years older than those with the least impairments. “To what degree were the observed sensory deficits linked to normal aging rather than dementia?”
As well, Dr. Rushworth pointed out that the molecular mechanisms that “kick-start” dementia are believed to occur in midlife – so possibly at an age younger than the study participants. “Do younger people of a ‘predementia’ age range display multisensory impairments?”
Because study participants could wear glasses during vision tests but were not allowed to wear hearing aids for the hearing tests, further standardization of sensory impairment is required, Dr. Rushworth said.
“Future studies will be essential in determining the value of clinical measurement of multisensory impairment as a possible dementia indicator and prevention strategy,” she concluded.
The study was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Alzheimer’s Association. Dr. Brenowitz and Dr. Rushworth have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.