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Study refines ALS risk among first-degree relatives of patients with disease
, according to a recent Irish population–based study.
Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).
Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.
For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.
In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.
Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.
The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”
Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.
“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”
Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.
SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.
, according to a recent Irish population–based study.
Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).
Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.
For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.
In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.
Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.
The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”
Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.
“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”
Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.
SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.
, according to a recent Irish population–based study.
Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).
Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.
For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.
In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.
Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.
The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”
Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.
“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”
Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.
SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.
FROM JAMA NEUROLOGY
Amitriptyline for chronic low back pain
Clinical question: Is a low-dose tricyclic antidepressant effective in the treatment of chronic low back pain?
Background: Lower back pain is the leading cause of disability globally and effective treatments are limited. Furthermore, opioid usage for lower back pain is a large contributor to the current opioid epidemic. A recent Cochrane review showed no clear evidence that antidepressant use in the treatment of back pain is effective, but it did note a lack of high-quality trials of sufficient rigor or length.
Study design: Double-blind, randomized controlled trial.
Setting: Single center trial in Melbourne.
Synopsis: Overall, 146 patients aged 18-75 with chronic lower back pain of no specific cause for more than 3 months were included. Exclusions included pathological cause, major coexisting illness, psychosis, or diagnosed depression. Patients were given amitriptyline 25 mg daily or benztropine mesylate 1 mg daily. Benztropine has similar anticholinergic side effects, without the antidepressant effect. Participants were assessed and followed by calls at 2 weeks, 1-2 months, 3 months, 4-5 months, and 6 months. Adherence was noted by the return of empty medication bottles at 6 months. Six-month surveys were completed by 81% and found that 70% of each group was adherent and 12% in each group withdrew because of adverse effects.
The primary outcome was level of pain at 6 months using a visual analog and descriptor scales. Secondary outcomes were measurement of disability, work missed, global improvement, general health, fear of movement, and depression.
The primary outcome was reduction in pain intensity of 12.6 (standard error, 2.7) with amitriptyline at 6 months, compared with 4.8 (SE 2.9) with benztropine, which did not meet statistical significance. There was a statistically significant difference in disability at 3 months, but not at 6 months.
Bottom line: This trial suggests that there may be a place for prescribed amitriptyline for chronic lower back pain, but it failed to show statistical significance. The study may not have been sufficiently powered to detect the difference.
Citations: Urquhart DM et al. Efficacy of low-dose amitriptyline for chronic low back pain: A randomized clinical trial. JAMA Intern Med. 2018;178(11):1474-81.
Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.
Clinical question: Is a low-dose tricyclic antidepressant effective in the treatment of chronic low back pain?
Background: Lower back pain is the leading cause of disability globally and effective treatments are limited. Furthermore, opioid usage for lower back pain is a large contributor to the current opioid epidemic. A recent Cochrane review showed no clear evidence that antidepressant use in the treatment of back pain is effective, but it did note a lack of high-quality trials of sufficient rigor or length.
Study design: Double-blind, randomized controlled trial.
Setting: Single center trial in Melbourne.
Synopsis: Overall, 146 patients aged 18-75 with chronic lower back pain of no specific cause for more than 3 months were included. Exclusions included pathological cause, major coexisting illness, psychosis, or diagnosed depression. Patients were given amitriptyline 25 mg daily or benztropine mesylate 1 mg daily. Benztropine has similar anticholinergic side effects, without the antidepressant effect. Participants were assessed and followed by calls at 2 weeks, 1-2 months, 3 months, 4-5 months, and 6 months. Adherence was noted by the return of empty medication bottles at 6 months. Six-month surveys were completed by 81% and found that 70% of each group was adherent and 12% in each group withdrew because of adverse effects.
The primary outcome was level of pain at 6 months using a visual analog and descriptor scales. Secondary outcomes were measurement of disability, work missed, global improvement, general health, fear of movement, and depression.
The primary outcome was reduction in pain intensity of 12.6 (standard error, 2.7) with amitriptyline at 6 months, compared with 4.8 (SE 2.9) with benztropine, which did not meet statistical significance. There was a statistically significant difference in disability at 3 months, but not at 6 months.
Bottom line: This trial suggests that there may be a place for prescribed amitriptyline for chronic lower back pain, but it failed to show statistical significance. The study may not have been sufficiently powered to detect the difference.
Citations: Urquhart DM et al. Efficacy of low-dose amitriptyline for chronic low back pain: A randomized clinical trial. JAMA Intern Med. 2018;178(11):1474-81.
Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.
Clinical question: Is a low-dose tricyclic antidepressant effective in the treatment of chronic low back pain?
Background: Lower back pain is the leading cause of disability globally and effective treatments are limited. Furthermore, opioid usage for lower back pain is a large contributor to the current opioid epidemic. A recent Cochrane review showed no clear evidence that antidepressant use in the treatment of back pain is effective, but it did note a lack of high-quality trials of sufficient rigor or length.
Study design: Double-blind, randomized controlled trial.
Setting: Single center trial in Melbourne.
Synopsis: Overall, 146 patients aged 18-75 with chronic lower back pain of no specific cause for more than 3 months were included. Exclusions included pathological cause, major coexisting illness, psychosis, or diagnosed depression. Patients were given amitriptyline 25 mg daily or benztropine mesylate 1 mg daily. Benztropine has similar anticholinergic side effects, without the antidepressant effect. Participants were assessed and followed by calls at 2 weeks, 1-2 months, 3 months, 4-5 months, and 6 months. Adherence was noted by the return of empty medication bottles at 6 months. Six-month surveys were completed by 81% and found that 70% of each group was adherent and 12% in each group withdrew because of adverse effects.
The primary outcome was level of pain at 6 months using a visual analog and descriptor scales. Secondary outcomes were measurement of disability, work missed, global improvement, general health, fear of movement, and depression.
The primary outcome was reduction in pain intensity of 12.6 (standard error, 2.7) with amitriptyline at 6 months, compared with 4.8 (SE 2.9) with benztropine, which did not meet statistical significance. There was a statistically significant difference in disability at 3 months, but not at 6 months.
Bottom line: This trial suggests that there may be a place for prescribed amitriptyline for chronic lower back pain, but it failed to show statistical significance. The study may not have been sufficiently powered to detect the difference.
Citations: Urquhart DM et al. Efficacy of low-dose amitriptyline for chronic low back pain: A randomized clinical trial. JAMA Intern Med. 2018;178(11):1474-81.
Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.
Liberalized low–glycemic-index diet effective for seizure reduction
BANGKOK – in a randomized, double-blind, 24-week, noninferiority study.
The low–glycemic-index diet (LGID) was introduced as a kinder, gentler, variant of the classic ketogenic diet for seizure frequency reduction. The ketogenic diet’s efficacy for this purpose is well established, but compliance is a problem and discontinuation rates are high. Yet even though the LGID was designed to be less onerous than the ketogenic diet, many children and parents also find the 7-days-a-week LGID to be excessively burdensome. This was the impetus for pitting the daily LGID against an intermittent version – 5 days on, 2 days off – in a randomized trial, Prateek K. Panda, MD, explained at the International Epilepsy Congress.
The hypothesis of this noninferiority trial was that adherence to the liberalized LGID would be similar to or better than that with the daily LGID regimen, with resultant similar reductions in seizure frequency. And further, that patients on the intermittent LGID would feel better because it would help improve depleted glycogen stores important for daily activity and that the liberalized diet would also be rated more favorably by caregivers, Dr. Panda said at the congress sponsored by the International League Against Epilepsy.
The 24-week, single-center trial included 122 children ages 1-15 years with drug-resistant epilepsy. At baseline they averaged 99 seizures per week by parental diary despite being on a median of four antiepileptic drugs. A total of 88% of participants had some form of structural epilepsy; the rest had a probable or confirmed genetic cause for their seizure disorder, according to Dr. Panda of the All-India Institute of Medical Sciences in New Delhi.
The standard daily LGID was comprised of 10% carbohydrate, 30% protein, and 60% fat, with only low–glycemic-index foods permitted. The cohort randomized to the liberalized diet ate that way on weekdays; however, on Saturdays and Sundays their diet was 20% carbohydrate, 30% protein, and 50% fat, with both medium- and low–glycemic-index foods allowed.
The primary outcome was the mean reduction in seizures per week by caregiver records at 24 weeks. The reduction from baseline was 54% in the strict LGID group and not significantly different at 49% in the intermittent LGID patients. Overall, 54% of patients in the strict LGID arm experienced a greater than 50% reduction in weekly seizure frequency, as did 50% on the liberalized diet, a nonsignificant difference.
There were five study dropouts in the strict LGID group and three in the liberalized LGID cohort. The two groups showed similar improvements over baseline in measures of social function, behavior, and cognition. Parents of children in the liberalized LGID group rated that diet as significantly less difficult to administer than those randomized to the strict LGID therapy.
Mean hemoglobin A1c improved in the strict LGID patients from 5.7% at baseline to 5.1% at both 12 and 24 weeks. The intermittent LGID group went from 5.6% to 5.0% and then to 5.2%. There was no correlation between HbA1c and reduction in seizure frequency. In contrast, serum beta-hydroxybutyrate levels showed a moderate correlation with seizure frequency, a novel finding which if confirmed might render beta-hydroxybutyrate useful as a biomarker, according to Dr. Panda.
Adverse events – mostly dyslipidemia and GI complaints such as vomiting or constipation – occurred in 25% of the strict LGID group and 13% with the intermittent LGID. All adverse events were mild.
Dr. Panda reported having no financial conflicts regarding the study, sponsored by the All-India Institute of Medical Sciences.
SOURCE: Panda PK et al. IEC 2019, Abstract P056.
BANGKOK – in a randomized, double-blind, 24-week, noninferiority study.
The low–glycemic-index diet (LGID) was introduced as a kinder, gentler, variant of the classic ketogenic diet for seizure frequency reduction. The ketogenic diet’s efficacy for this purpose is well established, but compliance is a problem and discontinuation rates are high. Yet even though the LGID was designed to be less onerous than the ketogenic diet, many children and parents also find the 7-days-a-week LGID to be excessively burdensome. This was the impetus for pitting the daily LGID against an intermittent version – 5 days on, 2 days off – in a randomized trial, Prateek K. Panda, MD, explained at the International Epilepsy Congress.
The hypothesis of this noninferiority trial was that adherence to the liberalized LGID would be similar to or better than that with the daily LGID regimen, with resultant similar reductions in seizure frequency. And further, that patients on the intermittent LGID would feel better because it would help improve depleted glycogen stores important for daily activity and that the liberalized diet would also be rated more favorably by caregivers, Dr. Panda said at the congress sponsored by the International League Against Epilepsy.
The 24-week, single-center trial included 122 children ages 1-15 years with drug-resistant epilepsy. At baseline they averaged 99 seizures per week by parental diary despite being on a median of four antiepileptic drugs. A total of 88% of participants had some form of structural epilepsy; the rest had a probable or confirmed genetic cause for their seizure disorder, according to Dr. Panda of the All-India Institute of Medical Sciences in New Delhi.
The standard daily LGID was comprised of 10% carbohydrate, 30% protein, and 60% fat, with only low–glycemic-index foods permitted. The cohort randomized to the liberalized diet ate that way on weekdays; however, on Saturdays and Sundays their diet was 20% carbohydrate, 30% protein, and 50% fat, with both medium- and low–glycemic-index foods allowed.
The primary outcome was the mean reduction in seizures per week by caregiver records at 24 weeks. The reduction from baseline was 54% in the strict LGID group and not significantly different at 49% in the intermittent LGID patients. Overall, 54% of patients in the strict LGID arm experienced a greater than 50% reduction in weekly seizure frequency, as did 50% on the liberalized diet, a nonsignificant difference.
There were five study dropouts in the strict LGID group and three in the liberalized LGID cohort. The two groups showed similar improvements over baseline in measures of social function, behavior, and cognition. Parents of children in the liberalized LGID group rated that diet as significantly less difficult to administer than those randomized to the strict LGID therapy.
Mean hemoglobin A1c improved in the strict LGID patients from 5.7% at baseline to 5.1% at both 12 and 24 weeks. The intermittent LGID group went from 5.6% to 5.0% and then to 5.2%. There was no correlation between HbA1c and reduction in seizure frequency. In contrast, serum beta-hydroxybutyrate levels showed a moderate correlation with seizure frequency, a novel finding which if confirmed might render beta-hydroxybutyrate useful as a biomarker, according to Dr. Panda.
Adverse events – mostly dyslipidemia and GI complaints such as vomiting or constipation – occurred in 25% of the strict LGID group and 13% with the intermittent LGID. All adverse events were mild.
Dr. Panda reported having no financial conflicts regarding the study, sponsored by the All-India Institute of Medical Sciences.
SOURCE: Panda PK et al. IEC 2019, Abstract P056.
BANGKOK – in a randomized, double-blind, 24-week, noninferiority study.
The low–glycemic-index diet (LGID) was introduced as a kinder, gentler, variant of the classic ketogenic diet for seizure frequency reduction. The ketogenic diet’s efficacy for this purpose is well established, but compliance is a problem and discontinuation rates are high. Yet even though the LGID was designed to be less onerous than the ketogenic diet, many children and parents also find the 7-days-a-week LGID to be excessively burdensome. This was the impetus for pitting the daily LGID against an intermittent version – 5 days on, 2 days off – in a randomized trial, Prateek K. Panda, MD, explained at the International Epilepsy Congress.
The hypothesis of this noninferiority trial was that adherence to the liberalized LGID would be similar to or better than that with the daily LGID regimen, with resultant similar reductions in seizure frequency. And further, that patients on the intermittent LGID would feel better because it would help improve depleted glycogen stores important for daily activity and that the liberalized diet would also be rated more favorably by caregivers, Dr. Panda said at the congress sponsored by the International League Against Epilepsy.
The 24-week, single-center trial included 122 children ages 1-15 years with drug-resistant epilepsy. At baseline they averaged 99 seizures per week by parental diary despite being on a median of four antiepileptic drugs. A total of 88% of participants had some form of structural epilepsy; the rest had a probable or confirmed genetic cause for their seizure disorder, according to Dr. Panda of the All-India Institute of Medical Sciences in New Delhi.
The standard daily LGID was comprised of 10% carbohydrate, 30% protein, and 60% fat, with only low–glycemic-index foods permitted. The cohort randomized to the liberalized diet ate that way on weekdays; however, on Saturdays and Sundays their diet was 20% carbohydrate, 30% protein, and 50% fat, with both medium- and low–glycemic-index foods allowed.
The primary outcome was the mean reduction in seizures per week by caregiver records at 24 weeks. The reduction from baseline was 54% in the strict LGID group and not significantly different at 49% in the intermittent LGID patients. Overall, 54% of patients in the strict LGID arm experienced a greater than 50% reduction in weekly seizure frequency, as did 50% on the liberalized diet, a nonsignificant difference.
There were five study dropouts in the strict LGID group and three in the liberalized LGID cohort. The two groups showed similar improvements over baseline in measures of social function, behavior, and cognition. Parents of children in the liberalized LGID group rated that diet as significantly less difficult to administer than those randomized to the strict LGID therapy.
Mean hemoglobin A1c improved in the strict LGID patients from 5.7% at baseline to 5.1% at both 12 and 24 weeks. The intermittent LGID group went from 5.6% to 5.0% and then to 5.2%. There was no correlation between HbA1c and reduction in seizure frequency. In contrast, serum beta-hydroxybutyrate levels showed a moderate correlation with seizure frequency, a novel finding which if confirmed might render beta-hydroxybutyrate useful as a biomarker, according to Dr. Panda.
Adverse events – mostly dyslipidemia and GI complaints such as vomiting or constipation – occurred in 25% of the strict LGID group and 13% with the intermittent LGID. All adverse events were mild.
Dr. Panda reported having no financial conflicts regarding the study, sponsored by the All-India Institute of Medical Sciences.
SOURCE: Panda PK et al. IEC 2019, Abstract P056.
REPORTING FROM IEC 2019
Medication overuse prevalent among U.S. migraine patients
PHILADELPHIA – according to findings from an analysis of 16,789 people with migraine.
About 18% of the people identified with migraine in the study cohort reported a drug consumption pattern that met the prespecified definition of “medication overuse,” Todd J. Schwedt, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. Supplying each migraine patient with a “comprehensive treatment plan” along with “improved acute treatment options ... may help reduce the prevalence and associated burden of medication overuse,” said Dr. Schwedt, a professor of neurology at the Mayo Clinic in Phoenix. The analysis also showed that medication overuse (MO) significantly linked with several markers of worse clinical status.
If patients have “an effective preventive treatment that reduces headaches and migraine attacks then they will, in general, use less acute medications. Many people with migraine never even get diagnosed, and patients who qualify for preventive treatment never get it,” Dr. Schwedt noted in an interview. He described a comprehensive treatment plan as a management strategy that includes lifestyle modifications, a migraine-prevention agent, and the availability of an effective acute treatment for a patient to use when a migraine strikes along with clear instructions on how to appropriately self-administer the medication. Only a small fraction of U.S. migraine patients currently receive this complete package of care, he said.
The analysis he ran used data collected in the CaMEO (Chronic Migraine Epidemiology and Outcomes) study, which used an Internet-based survey to collect data from a representative 58,000-person sample of U.S. residents, which included 16,789 who met the applied migraine definition, with 91% having fewer than 15 headaches/month and the remaining 9% with a monthly headache average of 15 or more (Cephalagia. 2015 Jun;35[7]:563-78).
The researchers defined overuse of a single medication as use 15 times or more a month of an NSAID, aspirin, or acetaminophen, or use at least 10 times a month of a triptan, ergotamine, or opioid. They also had a prespecified definition of multidrug overuse that applied similar monthly thresholds. The patients averaged about 41 years old, three-quarters were women, and 85% were white. Patients identified with MO had a substantially higher rate of headaches per month: an average of nearly 12, compared with an average of about 4 per month among those without overuse. Almost two-thirds of the patients with MO reported having been formally diagnosed as having migraine headaches, compared with 41% of those without overuse.
Among the 13,749 patients (82%) on some headache medication, 67% were on a nonopioid analgesic, including 61% on an NSAID. MO among all people on nonopioid analgesics was 16%, and 12% among those who used NSAIDS. The most overused drug in this subgroup were combination analgesics, overused by 18% of those taking these drugs.
The drug class with the biggest MO rate was opioids, used by 12% of those on any medication and overused by 22% of those taking an opioid. Triptans were taken by 11%, with an MO rate of 11% among these users. Ergotamine was used by less than 1% of all patients, and those taking this drug tallied a 19% MO rate.
“Opioids were the class most often overused, more evidence that opioids should rarely if ever be used to treat migraine,” Dr. Schwedt said.
The analysis also showed that patients who had MO has multiple signs of worse clinical status. Patients with MO had a significantly higher rate of diagnosed depression, 54%, compared with 28% in those without MO; anxiety, 49% compared with 26%; migraine-associated disability, 73% compared with 32%; migraine-associated functional impairment (Migraine Interictal Burden Scale), 65% compared with 32%; and emergency department or urgent care use, 13% compared with 3%. All these between-group differences were statistically significant.
CaMEO was funded by Allergan. Dr. Schwedt has been a consultant to Allergan, and also to Alder, Amgen, Cipla, Dr. Reddy’s, Ipsen, Lilly, Novartis, and Teva. He has stock ownership in Aural Analytics, Nocira, and Second Opinion, and he has received research funding from Amgen.
SOURCE: Schwedt TJ et al. Headache. 2019 June;59[S1]:83-4, Abstract P92.
PHILADELPHIA – according to findings from an analysis of 16,789 people with migraine.
About 18% of the people identified with migraine in the study cohort reported a drug consumption pattern that met the prespecified definition of “medication overuse,” Todd J. Schwedt, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. Supplying each migraine patient with a “comprehensive treatment plan” along with “improved acute treatment options ... may help reduce the prevalence and associated burden of medication overuse,” said Dr. Schwedt, a professor of neurology at the Mayo Clinic in Phoenix. The analysis also showed that medication overuse (MO) significantly linked with several markers of worse clinical status.
If patients have “an effective preventive treatment that reduces headaches and migraine attacks then they will, in general, use less acute medications. Many people with migraine never even get diagnosed, and patients who qualify for preventive treatment never get it,” Dr. Schwedt noted in an interview. He described a comprehensive treatment plan as a management strategy that includes lifestyle modifications, a migraine-prevention agent, and the availability of an effective acute treatment for a patient to use when a migraine strikes along with clear instructions on how to appropriately self-administer the medication. Only a small fraction of U.S. migraine patients currently receive this complete package of care, he said.
The analysis he ran used data collected in the CaMEO (Chronic Migraine Epidemiology and Outcomes) study, which used an Internet-based survey to collect data from a representative 58,000-person sample of U.S. residents, which included 16,789 who met the applied migraine definition, with 91% having fewer than 15 headaches/month and the remaining 9% with a monthly headache average of 15 or more (Cephalagia. 2015 Jun;35[7]:563-78).
The researchers defined overuse of a single medication as use 15 times or more a month of an NSAID, aspirin, or acetaminophen, or use at least 10 times a month of a triptan, ergotamine, or opioid. They also had a prespecified definition of multidrug overuse that applied similar monthly thresholds. The patients averaged about 41 years old, three-quarters were women, and 85% were white. Patients identified with MO had a substantially higher rate of headaches per month: an average of nearly 12, compared with an average of about 4 per month among those without overuse. Almost two-thirds of the patients with MO reported having been formally diagnosed as having migraine headaches, compared with 41% of those without overuse.
Among the 13,749 patients (82%) on some headache medication, 67% were on a nonopioid analgesic, including 61% on an NSAID. MO among all people on nonopioid analgesics was 16%, and 12% among those who used NSAIDS. The most overused drug in this subgroup were combination analgesics, overused by 18% of those taking these drugs.
The drug class with the biggest MO rate was opioids, used by 12% of those on any medication and overused by 22% of those taking an opioid. Triptans were taken by 11%, with an MO rate of 11% among these users. Ergotamine was used by less than 1% of all patients, and those taking this drug tallied a 19% MO rate.
“Opioids were the class most often overused, more evidence that opioids should rarely if ever be used to treat migraine,” Dr. Schwedt said.
The analysis also showed that patients who had MO has multiple signs of worse clinical status. Patients with MO had a significantly higher rate of diagnosed depression, 54%, compared with 28% in those without MO; anxiety, 49% compared with 26%; migraine-associated disability, 73% compared with 32%; migraine-associated functional impairment (Migraine Interictal Burden Scale), 65% compared with 32%; and emergency department or urgent care use, 13% compared with 3%. All these between-group differences were statistically significant.
CaMEO was funded by Allergan. Dr. Schwedt has been a consultant to Allergan, and also to Alder, Amgen, Cipla, Dr. Reddy’s, Ipsen, Lilly, Novartis, and Teva. He has stock ownership in Aural Analytics, Nocira, and Second Opinion, and he has received research funding from Amgen.
SOURCE: Schwedt TJ et al. Headache. 2019 June;59[S1]:83-4, Abstract P92.
PHILADELPHIA – according to findings from an analysis of 16,789 people with migraine.
About 18% of the people identified with migraine in the study cohort reported a drug consumption pattern that met the prespecified definition of “medication overuse,” Todd J. Schwedt, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. Supplying each migraine patient with a “comprehensive treatment plan” along with “improved acute treatment options ... may help reduce the prevalence and associated burden of medication overuse,” said Dr. Schwedt, a professor of neurology at the Mayo Clinic in Phoenix. The analysis also showed that medication overuse (MO) significantly linked with several markers of worse clinical status.
If patients have “an effective preventive treatment that reduces headaches and migraine attacks then they will, in general, use less acute medications. Many people with migraine never even get diagnosed, and patients who qualify for preventive treatment never get it,” Dr. Schwedt noted in an interview. He described a comprehensive treatment plan as a management strategy that includes lifestyle modifications, a migraine-prevention agent, and the availability of an effective acute treatment for a patient to use when a migraine strikes along with clear instructions on how to appropriately self-administer the medication. Only a small fraction of U.S. migraine patients currently receive this complete package of care, he said.
The analysis he ran used data collected in the CaMEO (Chronic Migraine Epidemiology and Outcomes) study, which used an Internet-based survey to collect data from a representative 58,000-person sample of U.S. residents, which included 16,789 who met the applied migraine definition, with 91% having fewer than 15 headaches/month and the remaining 9% with a monthly headache average of 15 or more (Cephalagia. 2015 Jun;35[7]:563-78).
The researchers defined overuse of a single medication as use 15 times or more a month of an NSAID, aspirin, or acetaminophen, or use at least 10 times a month of a triptan, ergotamine, or opioid. They also had a prespecified definition of multidrug overuse that applied similar monthly thresholds. The patients averaged about 41 years old, three-quarters were women, and 85% were white. Patients identified with MO had a substantially higher rate of headaches per month: an average of nearly 12, compared with an average of about 4 per month among those without overuse. Almost two-thirds of the patients with MO reported having been formally diagnosed as having migraine headaches, compared with 41% of those without overuse.
Among the 13,749 patients (82%) on some headache medication, 67% were on a nonopioid analgesic, including 61% on an NSAID. MO among all people on nonopioid analgesics was 16%, and 12% among those who used NSAIDS. The most overused drug in this subgroup were combination analgesics, overused by 18% of those taking these drugs.
The drug class with the biggest MO rate was opioids, used by 12% of those on any medication and overused by 22% of those taking an opioid. Triptans were taken by 11%, with an MO rate of 11% among these users. Ergotamine was used by less than 1% of all patients, and those taking this drug tallied a 19% MO rate.
“Opioids were the class most often overused, more evidence that opioids should rarely if ever be used to treat migraine,” Dr. Schwedt said.
The analysis also showed that patients who had MO has multiple signs of worse clinical status. Patients with MO had a significantly higher rate of diagnosed depression, 54%, compared with 28% in those without MO; anxiety, 49% compared with 26%; migraine-associated disability, 73% compared with 32%; migraine-associated functional impairment (Migraine Interictal Burden Scale), 65% compared with 32%; and emergency department or urgent care use, 13% compared with 3%. All these between-group differences were statistically significant.
CaMEO was funded by Allergan. Dr. Schwedt has been a consultant to Allergan, and also to Alder, Amgen, Cipla, Dr. Reddy’s, Ipsen, Lilly, Novartis, and Teva. He has stock ownership in Aural Analytics, Nocira, and Second Opinion, and he has received research funding from Amgen.
SOURCE: Schwedt TJ et al. Headache. 2019 June;59[S1]:83-4, Abstract P92.
REPORTING FROM AHS 2019
When’s the right time to use dementia as a diagnosis?
Is dementia a diagnosis?
I use it myself, although I find that some neurologists consider this blasphemy.
The problem is that there aren’t many terms to cover cognitive disorders beyond mild cognitive impairment (MCI). Phrases like “cortical degeneration” and “frontotemporal disorder” are difficult for families and patients. They aren’t medically trained and want something easy to write down.
“Alzheimer’s,” or – as one patient’s family member says, “the A-word” – is often more accurate, but has stigma attached to it that many don’t want, especially at a first visit. It also immediately conjures up feared images of nursing homes, wheelchairs, and bed-bound people.
So I use a diagnosis of dementia with many families, at least initially. Since, with occasional exceptions, we tend to perform a work-up of all cognitive disorders the same way, I don’t have a problem with using a more generic blanket term. As I sometimes try to simplify things, I’ll say, “It’s like squares and rectangles. Alzheimer’s disease is a dementia, but not all dementias are Alzheimer’s disease.”
I don’t do this to avoid confrontation, be dishonest, mislead patients and families, or avoid telling the truth. I still make it very clear that this is a progressive neurologic illness that will cause worsening cognitive problems over time. But many times families aren’t ready for “the A-word” early on, or there’s a concern the patient will harm themselves while they still have that capacity. Sometimes, it’s better to use a different phrase.
It may all be semantics, but on a personal level, a word can make a huge difference.
So I say dementia. In spite of some editorials I’ve seen saying we should retire the phrase, I argue that in many circumstances it’s still valid and useful.
It may not be a final, or even specific, diagnosis, but it is often the best and most socially acceptable one at the beginning of the doctor-patient-family relationship. When you’re trying to build rapport with them, that’s equally critical when you know what’s to come down the road.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Is dementia a diagnosis?
I use it myself, although I find that some neurologists consider this blasphemy.
The problem is that there aren’t many terms to cover cognitive disorders beyond mild cognitive impairment (MCI). Phrases like “cortical degeneration” and “frontotemporal disorder” are difficult for families and patients. They aren’t medically trained and want something easy to write down.
“Alzheimer’s,” or – as one patient’s family member says, “the A-word” – is often more accurate, but has stigma attached to it that many don’t want, especially at a first visit. It also immediately conjures up feared images of nursing homes, wheelchairs, and bed-bound people.
So I use a diagnosis of dementia with many families, at least initially. Since, with occasional exceptions, we tend to perform a work-up of all cognitive disorders the same way, I don’t have a problem with using a more generic blanket term. As I sometimes try to simplify things, I’ll say, “It’s like squares and rectangles. Alzheimer’s disease is a dementia, but not all dementias are Alzheimer’s disease.”
I don’t do this to avoid confrontation, be dishonest, mislead patients and families, or avoid telling the truth. I still make it very clear that this is a progressive neurologic illness that will cause worsening cognitive problems over time. But many times families aren’t ready for “the A-word” early on, or there’s a concern the patient will harm themselves while they still have that capacity. Sometimes, it’s better to use a different phrase.
It may all be semantics, but on a personal level, a word can make a huge difference.
So I say dementia. In spite of some editorials I’ve seen saying we should retire the phrase, I argue that in many circumstances it’s still valid and useful.
It may not be a final, or even specific, diagnosis, but it is often the best and most socially acceptable one at the beginning of the doctor-patient-family relationship. When you’re trying to build rapport with them, that’s equally critical when you know what’s to come down the road.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Is dementia a diagnosis?
I use it myself, although I find that some neurologists consider this blasphemy.
The problem is that there aren’t many terms to cover cognitive disorders beyond mild cognitive impairment (MCI). Phrases like “cortical degeneration” and “frontotemporal disorder” are difficult for families and patients. They aren’t medically trained and want something easy to write down.
“Alzheimer’s,” or – as one patient’s family member says, “the A-word” – is often more accurate, but has stigma attached to it that many don’t want, especially at a first visit. It also immediately conjures up feared images of nursing homes, wheelchairs, and bed-bound people.
So I use a diagnosis of dementia with many families, at least initially. Since, with occasional exceptions, we tend to perform a work-up of all cognitive disorders the same way, I don’t have a problem with using a more generic blanket term. As I sometimes try to simplify things, I’ll say, “It’s like squares and rectangles. Alzheimer’s disease is a dementia, but not all dementias are Alzheimer’s disease.”
I don’t do this to avoid confrontation, be dishonest, mislead patients and families, or avoid telling the truth. I still make it very clear that this is a progressive neurologic illness that will cause worsening cognitive problems over time. But many times families aren’t ready for “the A-word” early on, or there’s a concern the patient will harm themselves while they still have that capacity. Sometimes, it’s better to use a different phrase.
It may all be semantics, but on a personal level, a word can make a huge difference.
So I say dementia. In spite of some editorials I’ve seen saying we should retire the phrase, I argue that in many circumstances it’s still valid and useful.
It may not be a final, or even specific, diagnosis, but it is often the best and most socially acceptable one at the beginning of the doctor-patient-family relationship. When you’re trying to build rapport with them, that’s equally critical when you know what’s to come down the road.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Statins crush early seizure risk poststroke
BANGKOK – Statin therapy, even when initiated only upon hospitalization for acute ischemic stroke, was associated with a striking reduction in the risk of early poststroke symptomatic seizure in a large observational study.
Using propensity-score matching to control for potential confounders, use of a statin during acute stroke management was associated with a “robust” 77% reduction in the risk of developing a symptomatic seizure within 7 days after hospital admission, Soichiro Matsubara, MD, reported at the International Epilepsy Congress.
This is an important finding because early symptomatic seizure (ESS) occurs in 2%-7% of patients following an acute ischemic stroke. Moreover, an Italian meta-analysis concluded that ESS was associated with a 4.4-fold increased risk of developing poststroke epilepsy (Epilepsia. 2016 Aug;57[8]:1205-14), noted Dr. Matsubara, a neurologist at the National Cerebral and Cardiovascular Center in Suita, Japan, as well as at Kumamoto (Japan) University.
He presented a study of 2,969 consecutive acute ischemic stroke patients with no history of epilepsy who were admitted to the Japanese comprehensive stroke center, of whom 2.2% experienced ESS. At physician discretion, 19% of the ESS cohort were on a statin during their acute stroke management, as were 55% of the no-ESS group. Four-fifths of patients on a statin initiated the drug only upon hospital admission.
Strokes tended to be more severe in the ESS group, with a median initial National Institutes of Health Stroke Scale score of 12.5, compared with 4 in the seizure-free patients. A cortical stroke lesion was evident upon imaging in 89% of the ESS group and 55% of no-ESS patients. Among ESS patients, 46% had a cardiometabolic stroke, compared with 34% of the no-ESS cohort. Mean C-reactive protein levels and white blood cell counts were significantly higher in the ESS cohort as well. Their median hospital length of stay was 25.5 days, versus 18 days in the no-ESS group, Dr. Matsubara said at the congress sponsored by the International League Against Epilepsy.
Of the 76 ESSs that occurred in 66 patients, 37% were focal awareness seizures, 35% were focal to bilateral tonic-clonic seizures, and 28% were focal impaired awareness seizures.
In a multivariate analysis adjusted for age, sex, body mass index, stroke subtype, and other potential confounders, statin therapy during acute management of stroke was independently associated with a 56% reduction in the relative risk of ESS. In contrast, a cortical stroke lesion was associated with a 2.83-fold increased risk.
Since this wasn’t a randomized trial of statin therapy, Dr. Matsubara and his coinvestigators felt the need to go further in analyzing the data. After extensive propensity score matching for atrial fibrillation, current smoking, systolic blood pressure, the presence or absence of a cortical stroke lesion, large vessel stenosis, and other possible confounders, they were left with two closely comparable groups: 886 statin-treated stroke patients and an equal number who were not on statin therapy during their acute stroke management. The key finding: The risk of ESS was reduced by a whopping 77% in the patients on statin therapy.
The neurologist observed that these new findings in acute ischemic stroke patients are consistent with an earlier study in a U.S. Veterans Affairs population, which demonstrated that statin therapy was associated with a significantly lower risk of new-onset geriatric epilepsy (J Am Geriatr Soc. 2009 Feb;57[2]:237-42).
As to the possible mechanism by which statins may protect against ESS, Dr. Matsubara noted that acute ischemic stroke causes toxic neuronal excitation because of blood-brain barrier disruption, ion channel dysfunction, altered gene expression, and increased release of neurotransmitters. In animal models, statins provide a neuroprotective effect by reducing glutamate levels, activating endothelial nitric oxide synthase, and inhibiting production of interleukin-6, tumor necrosis factor-alpha, and other inflammatory cytokines.
Asked about the intensity of the statin therapy, Dr. Matsubara replied that the target was typically an LDL cholesterol below 100 mg/dL.
He reported having no financial conflicts regarding the study, conducted free of commercial support.
SOURCE: Matsubara S et al. IEC 219, Abstract P002.
BANGKOK – Statin therapy, even when initiated only upon hospitalization for acute ischemic stroke, was associated with a striking reduction in the risk of early poststroke symptomatic seizure in a large observational study.
Using propensity-score matching to control for potential confounders, use of a statin during acute stroke management was associated with a “robust” 77% reduction in the risk of developing a symptomatic seizure within 7 days after hospital admission, Soichiro Matsubara, MD, reported at the International Epilepsy Congress.
This is an important finding because early symptomatic seizure (ESS) occurs in 2%-7% of patients following an acute ischemic stroke. Moreover, an Italian meta-analysis concluded that ESS was associated with a 4.4-fold increased risk of developing poststroke epilepsy (Epilepsia. 2016 Aug;57[8]:1205-14), noted Dr. Matsubara, a neurologist at the National Cerebral and Cardiovascular Center in Suita, Japan, as well as at Kumamoto (Japan) University.
He presented a study of 2,969 consecutive acute ischemic stroke patients with no history of epilepsy who were admitted to the Japanese comprehensive stroke center, of whom 2.2% experienced ESS. At physician discretion, 19% of the ESS cohort were on a statin during their acute stroke management, as were 55% of the no-ESS group. Four-fifths of patients on a statin initiated the drug only upon hospital admission.
Strokes tended to be more severe in the ESS group, with a median initial National Institutes of Health Stroke Scale score of 12.5, compared with 4 in the seizure-free patients. A cortical stroke lesion was evident upon imaging in 89% of the ESS group and 55% of no-ESS patients. Among ESS patients, 46% had a cardiometabolic stroke, compared with 34% of the no-ESS cohort. Mean C-reactive protein levels and white blood cell counts were significantly higher in the ESS cohort as well. Their median hospital length of stay was 25.5 days, versus 18 days in the no-ESS group, Dr. Matsubara said at the congress sponsored by the International League Against Epilepsy.
Of the 76 ESSs that occurred in 66 patients, 37% were focal awareness seizures, 35% were focal to bilateral tonic-clonic seizures, and 28% were focal impaired awareness seizures.
In a multivariate analysis adjusted for age, sex, body mass index, stroke subtype, and other potential confounders, statin therapy during acute management of stroke was independently associated with a 56% reduction in the relative risk of ESS. In contrast, a cortical stroke lesion was associated with a 2.83-fold increased risk.
Since this wasn’t a randomized trial of statin therapy, Dr. Matsubara and his coinvestigators felt the need to go further in analyzing the data. After extensive propensity score matching for atrial fibrillation, current smoking, systolic blood pressure, the presence or absence of a cortical stroke lesion, large vessel stenosis, and other possible confounders, they were left with two closely comparable groups: 886 statin-treated stroke patients and an equal number who were not on statin therapy during their acute stroke management. The key finding: The risk of ESS was reduced by a whopping 77% in the patients on statin therapy.
The neurologist observed that these new findings in acute ischemic stroke patients are consistent with an earlier study in a U.S. Veterans Affairs population, which demonstrated that statin therapy was associated with a significantly lower risk of new-onset geriatric epilepsy (J Am Geriatr Soc. 2009 Feb;57[2]:237-42).
As to the possible mechanism by which statins may protect against ESS, Dr. Matsubara noted that acute ischemic stroke causes toxic neuronal excitation because of blood-brain barrier disruption, ion channel dysfunction, altered gene expression, and increased release of neurotransmitters. In animal models, statins provide a neuroprotective effect by reducing glutamate levels, activating endothelial nitric oxide synthase, and inhibiting production of interleukin-6, tumor necrosis factor-alpha, and other inflammatory cytokines.
Asked about the intensity of the statin therapy, Dr. Matsubara replied that the target was typically an LDL cholesterol below 100 mg/dL.
He reported having no financial conflicts regarding the study, conducted free of commercial support.
SOURCE: Matsubara S et al. IEC 219, Abstract P002.
BANGKOK – Statin therapy, even when initiated only upon hospitalization for acute ischemic stroke, was associated with a striking reduction in the risk of early poststroke symptomatic seizure in a large observational study.
Using propensity-score matching to control for potential confounders, use of a statin during acute stroke management was associated with a “robust” 77% reduction in the risk of developing a symptomatic seizure within 7 days after hospital admission, Soichiro Matsubara, MD, reported at the International Epilepsy Congress.
This is an important finding because early symptomatic seizure (ESS) occurs in 2%-7% of patients following an acute ischemic stroke. Moreover, an Italian meta-analysis concluded that ESS was associated with a 4.4-fold increased risk of developing poststroke epilepsy (Epilepsia. 2016 Aug;57[8]:1205-14), noted Dr. Matsubara, a neurologist at the National Cerebral and Cardiovascular Center in Suita, Japan, as well as at Kumamoto (Japan) University.
He presented a study of 2,969 consecutive acute ischemic stroke patients with no history of epilepsy who were admitted to the Japanese comprehensive stroke center, of whom 2.2% experienced ESS. At physician discretion, 19% of the ESS cohort were on a statin during their acute stroke management, as were 55% of the no-ESS group. Four-fifths of patients on a statin initiated the drug only upon hospital admission.
Strokes tended to be more severe in the ESS group, with a median initial National Institutes of Health Stroke Scale score of 12.5, compared with 4 in the seizure-free patients. A cortical stroke lesion was evident upon imaging in 89% of the ESS group and 55% of no-ESS patients. Among ESS patients, 46% had a cardiometabolic stroke, compared with 34% of the no-ESS cohort. Mean C-reactive protein levels and white blood cell counts were significantly higher in the ESS cohort as well. Their median hospital length of stay was 25.5 days, versus 18 days in the no-ESS group, Dr. Matsubara said at the congress sponsored by the International League Against Epilepsy.
Of the 76 ESSs that occurred in 66 patients, 37% were focal awareness seizures, 35% were focal to bilateral tonic-clonic seizures, and 28% were focal impaired awareness seizures.
In a multivariate analysis adjusted for age, sex, body mass index, stroke subtype, and other potential confounders, statin therapy during acute management of stroke was independently associated with a 56% reduction in the relative risk of ESS. In contrast, a cortical stroke lesion was associated with a 2.83-fold increased risk.
Since this wasn’t a randomized trial of statin therapy, Dr. Matsubara and his coinvestigators felt the need to go further in analyzing the data. After extensive propensity score matching for atrial fibrillation, current smoking, systolic blood pressure, the presence or absence of a cortical stroke lesion, large vessel stenosis, and other possible confounders, they were left with two closely comparable groups: 886 statin-treated stroke patients and an equal number who were not on statin therapy during their acute stroke management. The key finding: The risk of ESS was reduced by a whopping 77% in the patients on statin therapy.
The neurologist observed that these new findings in acute ischemic stroke patients are consistent with an earlier study in a U.S. Veterans Affairs population, which demonstrated that statin therapy was associated with a significantly lower risk of new-onset geriatric epilepsy (J Am Geriatr Soc. 2009 Feb;57[2]:237-42).
As to the possible mechanism by which statins may protect against ESS, Dr. Matsubara noted that acute ischemic stroke causes toxic neuronal excitation because of blood-brain barrier disruption, ion channel dysfunction, altered gene expression, and increased release of neurotransmitters. In animal models, statins provide a neuroprotective effect by reducing glutamate levels, activating endothelial nitric oxide synthase, and inhibiting production of interleukin-6, tumor necrosis factor-alpha, and other inflammatory cytokines.
Asked about the intensity of the statin therapy, Dr. Matsubara replied that the target was typically an LDL cholesterol below 100 mg/dL.
He reported having no financial conflicts regarding the study, conducted free of commercial support.
SOURCE: Matsubara S et al. IEC 219, Abstract P002.
REPORTING FROM IEC 2019
Gum bacteria and Alzheimer’s: A hypothesis inches forward
LOS ANGELES – Scientists testing an unusual hypothesis about the pathogenesis of Alzheimer’s disease say that use of an experimental antimicrobial drug to target a common oral infection was associated with biomarker improvements in people with the disease.
At the Alzheimer’s Association International Conference, Michael Detke, MD, PhD, of Cortexyme in South San Francisco, Calif., presented findings from a small cohort (n = 9) of people with mild to moderate Alzheimer’s disease (AD).
Six patients, mean age 72, were randomized to 4 weeks’ treatment with an agent called COR388, which inhibits toxic proteases produced by Porphyromonas gingivalis, a bacterium that colonizes the mouth and gums and has been found in the brains and cerebrospinal fluid of people with AD more than in non-AD patients. Another three subjects were randomized to placebo.
At 28 days, the CSF levels of an Alzheimer’s-associated apolipoprotein E (ApoE) fragment and serum levels of RANTES, a chemokine associated with chronic inflammation, were reduced from baseline by about one-third in treated subjects, compared with placebo subjects (P less than .05).
“In AD, ApoE is known to be fragmented and the fragments are known to be neurotoxic,” Dr. Detke, the lead study author, said in an interview. “We hypothesized that these P. gingivalis proteases may be acting on ApoE cleavage – so if you bind the proteases you should reduce the fragments. We saw in this study that ApoE fragment was reduced by 30%, or back to about normal levels.”
It is difficult to eradicate P. gingivalis infection using conventional antibiotics. The experimental agent COR388 “does not kill the bacteria but rather neutralizes it by binding to the proteases it produces, making the bacteria benign,” Dr. Detke said.
While hypotheses involving infectious causes of Alzheimer’s remain on the periphery of dementia research, Dr. Detke and his colleagues will soon be able to test theirs in a more meaningful way. At the conference, Dr. Detke presented detailed plans for a phase 2/3, placebo-controlled, clinical trial of COR388 in 570 patients aged 55-80 with mild to moderate AD.
Patients in the study are currently being randomized to 48 weeks of treatment with one of two doses, or placebo, with cognitive and biomarker endpoints planned, including for amyloid-beta, tau, and serum, plasma, and CSF markers of neuroinflammation.
Dr. Detke is an employee of Cortexyme, as are another 8 of the study’s 11 authors.
LOS ANGELES – Scientists testing an unusual hypothesis about the pathogenesis of Alzheimer’s disease say that use of an experimental antimicrobial drug to target a common oral infection was associated with biomarker improvements in people with the disease.
At the Alzheimer’s Association International Conference, Michael Detke, MD, PhD, of Cortexyme in South San Francisco, Calif., presented findings from a small cohort (n = 9) of people with mild to moderate Alzheimer’s disease (AD).
Six patients, mean age 72, were randomized to 4 weeks’ treatment with an agent called COR388, which inhibits toxic proteases produced by Porphyromonas gingivalis, a bacterium that colonizes the mouth and gums and has been found in the brains and cerebrospinal fluid of people with AD more than in non-AD patients. Another three subjects were randomized to placebo.
At 28 days, the CSF levels of an Alzheimer’s-associated apolipoprotein E (ApoE) fragment and serum levels of RANTES, a chemokine associated with chronic inflammation, were reduced from baseline by about one-third in treated subjects, compared with placebo subjects (P less than .05).
“In AD, ApoE is known to be fragmented and the fragments are known to be neurotoxic,” Dr. Detke, the lead study author, said in an interview. “We hypothesized that these P. gingivalis proteases may be acting on ApoE cleavage – so if you bind the proteases you should reduce the fragments. We saw in this study that ApoE fragment was reduced by 30%, or back to about normal levels.”
It is difficult to eradicate P. gingivalis infection using conventional antibiotics. The experimental agent COR388 “does not kill the bacteria but rather neutralizes it by binding to the proteases it produces, making the bacteria benign,” Dr. Detke said.
While hypotheses involving infectious causes of Alzheimer’s remain on the periphery of dementia research, Dr. Detke and his colleagues will soon be able to test theirs in a more meaningful way. At the conference, Dr. Detke presented detailed plans for a phase 2/3, placebo-controlled, clinical trial of COR388 in 570 patients aged 55-80 with mild to moderate AD.
Patients in the study are currently being randomized to 48 weeks of treatment with one of two doses, or placebo, with cognitive and biomarker endpoints planned, including for amyloid-beta, tau, and serum, plasma, and CSF markers of neuroinflammation.
Dr. Detke is an employee of Cortexyme, as are another 8 of the study’s 11 authors.
LOS ANGELES – Scientists testing an unusual hypothesis about the pathogenesis of Alzheimer’s disease say that use of an experimental antimicrobial drug to target a common oral infection was associated with biomarker improvements in people with the disease.
At the Alzheimer’s Association International Conference, Michael Detke, MD, PhD, of Cortexyme in South San Francisco, Calif., presented findings from a small cohort (n = 9) of people with mild to moderate Alzheimer’s disease (AD).
Six patients, mean age 72, were randomized to 4 weeks’ treatment with an agent called COR388, which inhibits toxic proteases produced by Porphyromonas gingivalis, a bacterium that colonizes the mouth and gums and has been found in the brains and cerebrospinal fluid of people with AD more than in non-AD patients. Another three subjects were randomized to placebo.
At 28 days, the CSF levels of an Alzheimer’s-associated apolipoprotein E (ApoE) fragment and serum levels of RANTES, a chemokine associated with chronic inflammation, were reduced from baseline by about one-third in treated subjects, compared with placebo subjects (P less than .05).
“In AD, ApoE is known to be fragmented and the fragments are known to be neurotoxic,” Dr. Detke, the lead study author, said in an interview. “We hypothesized that these P. gingivalis proteases may be acting on ApoE cleavage – so if you bind the proteases you should reduce the fragments. We saw in this study that ApoE fragment was reduced by 30%, or back to about normal levels.”
It is difficult to eradicate P. gingivalis infection using conventional antibiotics. The experimental agent COR388 “does not kill the bacteria but rather neutralizes it by binding to the proteases it produces, making the bacteria benign,” Dr. Detke said.
While hypotheses involving infectious causes of Alzheimer’s remain on the periphery of dementia research, Dr. Detke and his colleagues will soon be able to test theirs in a more meaningful way. At the conference, Dr. Detke presented detailed plans for a phase 2/3, placebo-controlled, clinical trial of COR388 in 570 patients aged 55-80 with mild to moderate AD.
Patients in the study are currently being randomized to 48 weeks of treatment with one of two doses, or placebo, with cognitive and biomarker endpoints planned, including for amyloid-beta, tau, and serum, plasma, and CSF markers of neuroinflammation.
Dr. Detke is an employee of Cortexyme, as are another 8 of the study’s 11 authors.
FROM AAIC 2019
Cutaneous reaction to AEDs? Think autoimmune epilepsy
BANGKOK – Cutaneous reactions to antiepileptic drugs in patients with chronic epilepsy suggest increased likelihood of an autoimmune element to their seizure disorder, Fernando Cendes, MD, PhD, reported at the International Epilepsy Congress.
“My recommendation based on our findings is that if you have a patient who has a history of skin reactions to AEDs [antiepileptic drugs], or who has psychosis, or who has a very strange response to antiepileptic medication – meaning that at some points they are refractory and at other points they are very well controlled – I think those patients are probably at risk for having an autoantibody,” he said at the congress sponsored by the International League Against Epilepsy.
Screening for autoantibodies in such patients is appropriate. However, there’s a caveat: “The thing is, we don’t have evidence that treating these autoantibodies with immunotherapy will have any benefit on seizure control in these patients. We don’t have that data yet, but we are looking into it,” according to Dr. Cendes, professor of neurology at the State University of Campinas (Brazil).
He presented a study of 221 consecutive adults with severe chronic refractory epilepsy as evidenced by a mean disease duration of nearly 29 years, with an average of 5.93 seizures per month. A total of 77% had a structural etiology for their epilepsy, in most cases hippocampal sclerosis. In 19% of patients, the etiology was unknown. Overall, 95% of subjects had focal epilepsy, and the remainder had generalized epilepsy. All underwent serum testing for a variety of antibodies against neuronal surface antigens that have been implicated in encephalitis, seizures, and/or psychosis. Those who tested positive then underwent confirmatory testing of their cerebrospinal fluid.
The impetus for this study, the neurologist explained, is that although it’s now well established that seizures are a common clinical expression of acute- and subacute-phase autoimmune encephalitis marked by neuronal autoantibodies, little is known about the relationship between chronic epilepsy and such antibodies.
Only five Brazilian patients with chronic epilepsy, or 2.2%, tested positive for autoantibodies, all of whom had mesial temporal lobe epilepsy with hippocampal sclerosis. This suggests a possible autoimmune etiology for hippocampal sclerosis. Three of the five patients had anti-N-methyl-D-aspartate receptor antibodies (anti-NMDA) and two had antiglutamic acid decarboxylate antibodies (anti-GAD). No one was positive for anti–leucine-rich glioma-inactivated 1 antibodies (anti-LGI1), anti–contactin-associated proteinlike 2 (anti-caspr2), anti-glutamate receptor antibodies (anti-AMPAr), or anti–gamma-aminobutyric acid receptor antibodies (anti-GABAr).
The autoantibody-negative and the much smaller autoantibody-positive groups didn’t differ significantly in terms of demographics, seizure frequency, disease duration, drug resistance, cognitive impairment, comorbid autoimmune conditions, or history of status epilepticus. Indeed, only two between-group differences were found: fluctuation in seizure control was an issue in 10.6% of autoantibody-negative and 40% of autoantibody-positive patients, and cutaneous adverse reactions to antiepileptic drugs were noted in 10.6% of antibody-negative and 60% of antibody-positive patients. Psychiatric comorbidities were present in 49.5% of autoantibody-negative patients as compared with 80% – that is, four of five – who were autoantibody-positive, a trend that didn’t achieve statistical significance.
Asked if he thinks the autoantibodies found in a small subset of patients with chronic epilepsy were a cause or an effect of repeated seizures for so long, Dr. Cendes replied, “That’s a very interesting question, and I don’t have an answer, actually. But if seizures trigger development of these antibodies – and remember, this population we’re talking about had many, many seizures over the years – I would expect antibodies to be more frequent than the figure we found.”
He reported having no financial conflicts regarding his study.
SOURCE: Watanabe N et al. IEC 2019, Abstract P004.
BANGKOK – Cutaneous reactions to antiepileptic drugs in patients with chronic epilepsy suggest increased likelihood of an autoimmune element to their seizure disorder, Fernando Cendes, MD, PhD, reported at the International Epilepsy Congress.
“My recommendation based on our findings is that if you have a patient who has a history of skin reactions to AEDs [antiepileptic drugs], or who has psychosis, or who has a very strange response to antiepileptic medication – meaning that at some points they are refractory and at other points they are very well controlled – I think those patients are probably at risk for having an autoantibody,” he said at the congress sponsored by the International League Against Epilepsy.
Screening for autoantibodies in such patients is appropriate. However, there’s a caveat: “The thing is, we don’t have evidence that treating these autoantibodies with immunotherapy will have any benefit on seizure control in these patients. We don’t have that data yet, but we are looking into it,” according to Dr. Cendes, professor of neurology at the State University of Campinas (Brazil).
He presented a study of 221 consecutive adults with severe chronic refractory epilepsy as evidenced by a mean disease duration of nearly 29 years, with an average of 5.93 seizures per month. A total of 77% had a structural etiology for their epilepsy, in most cases hippocampal sclerosis. In 19% of patients, the etiology was unknown. Overall, 95% of subjects had focal epilepsy, and the remainder had generalized epilepsy. All underwent serum testing for a variety of antibodies against neuronal surface antigens that have been implicated in encephalitis, seizures, and/or psychosis. Those who tested positive then underwent confirmatory testing of their cerebrospinal fluid.
The impetus for this study, the neurologist explained, is that although it’s now well established that seizures are a common clinical expression of acute- and subacute-phase autoimmune encephalitis marked by neuronal autoantibodies, little is known about the relationship between chronic epilepsy and such antibodies.
Only five Brazilian patients with chronic epilepsy, or 2.2%, tested positive for autoantibodies, all of whom had mesial temporal lobe epilepsy with hippocampal sclerosis. This suggests a possible autoimmune etiology for hippocampal sclerosis. Three of the five patients had anti-N-methyl-D-aspartate receptor antibodies (anti-NMDA) and two had antiglutamic acid decarboxylate antibodies (anti-GAD). No one was positive for anti–leucine-rich glioma-inactivated 1 antibodies (anti-LGI1), anti–contactin-associated proteinlike 2 (anti-caspr2), anti-glutamate receptor antibodies (anti-AMPAr), or anti–gamma-aminobutyric acid receptor antibodies (anti-GABAr).
The autoantibody-negative and the much smaller autoantibody-positive groups didn’t differ significantly in terms of demographics, seizure frequency, disease duration, drug resistance, cognitive impairment, comorbid autoimmune conditions, or history of status epilepticus. Indeed, only two between-group differences were found: fluctuation in seizure control was an issue in 10.6% of autoantibody-negative and 40% of autoantibody-positive patients, and cutaneous adverse reactions to antiepileptic drugs were noted in 10.6% of antibody-negative and 60% of antibody-positive patients. Psychiatric comorbidities were present in 49.5% of autoantibody-negative patients as compared with 80% – that is, four of five – who were autoantibody-positive, a trend that didn’t achieve statistical significance.
Asked if he thinks the autoantibodies found in a small subset of patients with chronic epilepsy were a cause or an effect of repeated seizures for so long, Dr. Cendes replied, “That’s a very interesting question, and I don’t have an answer, actually. But if seizures trigger development of these antibodies – and remember, this population we’re talking about had many, many seizures over the years – I would expect antibodies to be more frequent than the figure we found.”
He reported having no financial conflicts regarding his study.
SOURCE: Watanabe N et al. IEC 2019, Abstract P004.
BANGKOK – Cutaneous reactions to antiepileptic drugs in patients with chronic epilepsy suggest increased likelihood of an autoimmune element to their seizure disorder, Fernando Cendes, MD, PhD, reported at the International Epilepsy Congress.
“My recommendation based on our findings is that if you have a patient who has a history of skin reactions to AEDs [antiepileptic drugs], or who has psychosis, or who has a very strange response to antiepileptic medication – meaning that at some points they are refractory and at other points they are very well controlled – I think those patients are probably at risk for having an autoantibody,” he said at the congress sponsored by the International League Against Epilepsy.
Screening for autoantibodies in such patients is appropriate. However, there’s a caveat: “The thing is, we don’t have evidence that treating these autoantibodies with immunotherapy will have any benefit on seizure control in these patients. We don’t have that data yet, but we are looking into it,” according to Dr. Cendes, professor of neurology at the State University of Campinas (Brazil).
He presented a study of 221 consecutive adults with severe chronic refractory epilepsy as evidenced by a mean disease duration of nearly 29 years, with an average of 5.93 seizures per month. A total of 77% had a structural etiology for their epilepsy, in most cases hippocampal sclerosis. In 19% of patients, the etiology was unknown. Overall, 95% of subjects had focal epilepsy, and the remainder had generalized epilepsy. All underwent serum testing for a variety of antibodies against neuronal surface antigens that have been implicated in encephalitis, seizures, and/or psychosis. Those who tested positive then underwent confirmatory testing of their cerebrospinal fluid.
The impetus for this study, the neurologist explained, is that although it’s now well established that seizures are a common clinical expression of acute- and subacute-phase autoimmune encephalitis marked by neuronal autoantibodies, little is known about the relationship between chronic epilepsy and such antibodies.
Only five Brazilian patients with chronic epilepsy, or 2.2%, tested positive for autoantibodies, all of whom had mesial temporal lobe epilepsy with hippocampal sclerosis. This suggests a possible autoimmune etiology for hippocampal sclerosis. Three of the five patients had anti-N-methyl-D-aspartate receptor antibodies (anti-NMDA) and two had antiglutamic acid decarboxylate antibodies (anti-GAD). No one was positive for anti–leucine-rich glioma-inactivated 1 antibodies (anti-LGI1), anti–contactin-associated proteinlike 2 (anti-caspr2), anti-glutamate receptor antibodies (anti-AMPAr), or anti–gamma-aminobutyric acid receptor antibodies (anti-GABAr).
The autoantibody-negative and the much smaller autoantibody-positive groups didn’t differ significantly in terms of demographics, seizure frequency, disease duration, drug resistance, cognitive impairment, comorbid autoimmune conditions, or history of status epilepticus. Indeed, only two between-group differences were found: fluctuation in seizure control was an issue in 10.6% of autoantibody-negative and 40% of autoantibody-positive patients, and cutaneous adverse reactions to antiepileptic drugs were noted in 10.6% of antibody-negative and 60% of antibody-positive patients. Psychiatric comorbidities were present in 49.5% of autoantibody-negative patients as compared with 80% – that is, four of five – who were autoantibody-positive, a trend that didn’t achieve statistical significance.
Asked if he thinks the autoantibodies found in a small subset of patients with chronic epilepsy were a cause or an effect of repeated seizures for so long, Dr. Cendes replied, “That’s a very interesting question, and I don’t have an answer, actually. But if seizures trigger development of these antibodies – and remember, this population we’re talking about had many, many seizures over the years – I would expect antibodies to be more frequent than the figure we found.”
He reported having no financial conflicts regarding his study.
SOURCE: Watanabe N et al. IEC 2019, Abstract P004.
REPORTING FROM IEC 2019
Nearly 20% of migraineurs use opioids for migraine
PHILADELPHIA – People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.
Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.
To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.
The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.
“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.
Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.
There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.
Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.
Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.
PHILADELPHIA – People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.
Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.
To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.
The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.
“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.
Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.
There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.
Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.
Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.
PHILADELPHIA – People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.
Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.
To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.
The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.
“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.
Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.
There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.
Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.
Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.
EXPERT ANALYSIS FROM AHS 2019
A plurality of migraineurs seeks care from primary care physicians
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Headache Society.
The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.
Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.
Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.
The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).
Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.
Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.
Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Headache Society.
The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.
Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.
Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.
The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).
Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.
Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.
Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Headache Society.
The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.
Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.
Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.
The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).
Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.
Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.
Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.
REPORTING FROM AHS 2019